This document summarizes a study on the molecular modeling and simulation of the Acyl CoA synthetase enzyme of Mycobacterium leprae, the bacteria that causes leprosy. The study identified Acyl CoA synthetase as a potential drug target as it plays a key role in lipid metabolism and is essential for the bacteria's survival. It performed sequence analysis to find structural homology to other Acyl CoA synthetases. Molecular modeling was used to generate a predicted structural model of the enzyme, which contained conserved domains important for its catalytic function. The researchers concluded that emphasizing Acyl CoA synthetase as a drug target could help identify novel drugs to treat leprosy.
Biofield Treatment: An Alternative Approach to Combat Multidrug-Resistant Sus...Mahendra Kumar Trivedi
As biofield therapy is increasingly popular in biomedical heath care, so present study aimed to evaluate the impact of Mr. Trivedi’s biofield treatment on antimicrobial sensitivity, minimum inhibitory concentration (MIC), biochemical study, and biotype number of multidrug resistant strain of R. ornithinolytica.
Clinical use of botulinum toxins in oral and maxillofacial surgeryDrKamini Dadsena
Purified botulinum toxin (BTX) was the first bacterial toxin used as a medicine. Since its introduction into clinical use, over 30 years ago, it has become a versatile drug in various fields of medicine.
Its mechanism of inhibiting acetylcholine release at neuromuscular junctions following local injection is unique for the treatment of facial wrinkles.
Other dose-dependent anti-neuroinflammatory effects and vascular modulating properties have extended its spectrum of applications.
Presentation from the 2014 Waterloo iGEM team at the Giant Jamboree in Boston. Read more about Staphylocide, our microbe engineered to silence antiobiotic resistance, on our 2014 wiki: http://2014.igem.org/Team:Waterloo.
This presentation is also available on the iGEM website: http://2014.igem.org/files/presentation/Waterloo_Championship.pdf
Biofield Treatment: An Alternative Approach to Combat Multidrug-Resistant Sus...Mahendra Kumar Trivedi
As biofield therapy is increasingly popular in biomedical heath care, so present study aimed to evaluate the impact of Mr. Trivedi’s biofield treatment on antimicrobial sensitivity, minimum inhibitory concentration (MIC), biochemical study, and biotype number of multidrug resistant strain of R. ornithinolytica.
Clinical use of botulinum toxins in oral and maxillofacial surgeryDrKamini Dadsena
Purified botulinum toxin (BTX) was the first bacterial toxin used as a medicine. Since its introduction into clinical use, over 30 years ago, it has become a versatile drug in various fields of medicine.
Its mechanism of inhibiting acetylcholine release at neuromuscular junctions following local injection is unique for the treatment of facial wrinkles.
Other dose-dependent anti-neuroinflammatory effects and vascular modulating properties have extended its spectrum of applications.
Presentation from the 2014 Waterloo iGEM team at the Giant Jamboree in Boston. Read more about Staphylocide, our microbe engineered to silence antiobiotic resistance, on our 2014 wiki: http://2014.igem.org/Team:Waterloo.
This presentation is also available on the iGEM website: http://2014.igem.org/files/presentation/Waterloo_Championship.pdf
This is part of our project that aims to assess current state of anti-microbial resistance in Egypt with a specific focus on development of anti-parasitic drugs resistance in addition.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Medical Biotechnology and Genetics Journal - SciDocPublishersScidoc Publishers
International Journal of Medical Biotechnology & Genetics (IJMBG) ISSN: 2379-1020 is a comprehensive, peer reviewed journal devoted to Medical Biotechnology & Genetics. IJMBG, published by SciDocPublishers is an Open Access journal that includes high quality papers, which covers all major areas of Medical Biotechnology & Genetics. SciDocPublishers with its Open Access publication model spreads all the day-to-day developments and research to readers around the world.
IJMBG retains its interest in evolutionary research as an international journal dedicated to the latest advancement of Medical Biotechnology & Genetics. It provides a platform for Scientists and Academicians all over the world to promote, share, and discuss various new issues and developments in different areas of Medical Biotechnology & Genetics.
For more details: http://scidoc.org/medical-biotechnology-and-genetics.php
The concept of transferring genes to tissues for clinical applications has been discussed for nearly half a century, but the ability to manipulate genetic material via recombinant DNA technology has brought this goal to reality. ‘Gene Therapy’ covers both the research and clinical applications of the new genetic therapy techniques currently being developed. The application of molecular biology has revolutionized researchers understanding of many diseases and has been readily applied for diagnostic purposes. Now-a-day this is originally conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, gene therapy now is considered for many non–life-threatening conditions, including those adversely affecting a patient’s quality of life. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. It is not very far, the justifiable optimism that with increased biotechnological improvement, gene therapy will become a standard part of clinical practice.
Antimicrobial Susceptibility, Biochemical Characterization and Molecular Typi...wilhelm mendel
Pathogenic isolates of Klebsiella pneumoniae (K. pneumoniae), particularly the extended-spectrum β-lactamase (ESBL) producing strains, are mostly associated with the failure of antibiotic therapy in nosocomial infections. The present work was designed to evaluate the impact of Mr. Trivedi’s biofield energy treatment on phenotypic and genotypic characteristics of K. pneumoniae. The strain of K. pneumoniae bearing ATCC 15380 (American Type Culture Collection) was procured from the Bangalore Genei, in sealed pack and divided into control and treated groups. Treated group was subjected to Mr. Trivedi’s biofield energy treatment and analyzed for the antimicrobial susceptibility, minimum inhibitory concentration (MIC), biochemical reactions, and biotyping using automated MicroScan Walk-Away® system. Further, the effect of biofield treatment was also evaluated using Random Amplified Polymorphic DNA (RAPD) in order to determine their epidemiological relatedness and genetic characteristics of biofield treated K. pneumoniae samples. The antimicrobial susceptibility results showed an improve sensitivity (i.e. from intermediate to susceptible) of ampicillin/sulbactam and chloramphenicol, while altered sensitivity of cephalothin (i.e. from susceptible to intermediate) was also reported as compared to the control sample. The MIC value showed two-fold decrease in MIC value of ampicillin/sulbactam (i.e. 16/8 to ≤8/4 μg/mL) and chloramphenicol (i.e. 16 to ≤ 8 μg/mL) as compared to the control. The cephalothin showed two-folds change (i.e. ≤ 8 to 16 μg/mL) in the MIC value as compared with the control. Biofield treatment showed 9.09% alterations in biochemical reactions followed by a change in biotype number (7774 4272) in the treated group with respect to the control (7774 4274). Genetic fingerprinting was performed on control and treated samples using RAPD-PCR biomarkers, which showed an average range of 11 to 15% of polymorphism among the treated samples with respect to the control. These results suggested that Mr. Trivedi’s biofield energy treatment has a significant impact on K. pneumoniae.
Phenotyping and Genotyping Characteristics of Serratia MarcescensGru Marckel
A study was performed to evaluate the impact of biofield treatment on phenotyping and genotyping characteristics of S. marcescens. Visit here for more details.
Biochemical Monitoring of Detoxifying Enzyme Levels in Field Population of Mo...BRNSS Publication Hub
The major cause of resistance mechanism in mosquitoes is the detoxification and degradation of
insecticides by overproduction of various metabolic enzymes. Quantitative metabolic enzyme assays
of carboxylesterases (α and β), mixed function oxidases (MFO), and glutathione S-transferases (GST)
have been commonly used in the detection of insecticide resistance due to its sensitive nature even at low
frequencies. For the present study, larval strains of Culex quinquefasciatus Say and Aedes aegypti (L) were
collected from the Cochin Corporation, Kerala, India, and were assayed to organophosphate temephos
and carbamate propoxur. The resistance ratio of median lethal time for temephos and propoxur from the
field population of C. quinquefasciatus and A. aegypti is higher than the laboratory population. Elevated
levels of α and β esterase enzyme were observed with the ratio of 1.6 and 1.54 for C. quinquefasciatus
and 1.51 and 1.47 for A. aegypti. In Culex mosquitoes, 1.71, and in Aedes, 1.64 fold increase in GST
enzyme level and 1.38 and 1.3 fold increase for the MFO level determined. The study results revealed
the urgent needs of improving the vector control methods by introducing alternative techniques and
strategies against mosquitoes.
An Effect of Biofield Treatment on Multidrug-resistant Burkholderia cepacia: ...Mahendra Kumar Trivedi
Aim of the present study was to analyze the impact of biofield treatment on multidrug resistant B. cepacia. Clinicalsample of B. cepacia was divided into two groups i.e. control and biofield treated.
IJERA (International journal of Engineering Research and Applications) is International online, ... peer reviewed journal. For more detail or submit your article, please visit www.ijera.com
This is part of our project that aims to assess current state of anti-microbial resistance in Egypt with a specific focus on development of anti-parasitic drugs resistance in addition.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Medical Biotechnology and Genetics Journal - SciDocPublishersScidoc Publishers
International Journal of Medical Biotechnology & Genetics (IJMBG) ISSN: 2379-1020 is a comprehensive, peer reviewed journal devoted to Medical Biotechnology & Genetics. IJMBG, published by SciDocPublishers is an Open Access journal that includes high quality papers, which covers all major areas of Medical Biotechnology & Genetics. SciDocPublishers with its Open Access publication model spreads all the day-to-day developments and research to readers around the world.
IJMBG retains its interest in evolutionary research as an international journal dedicated to the latest advancement of Medical Biotechnology & Genetics. It provides a platform for Scientists and Academicians all over the world to promote, share, and discuss various new issues and developments in different areas of Medical Biotechnology & Genetics.
For more details: http://scidoc.org/medical-biotechnology-and-genetics.php
The concept of transferring genes to tissues for clinical applications has been discussed for nearly half a century, but the ability to manipulate genetic material via recombinant DNA technology has brought this goal to reality. ‘Gene Therapy’ covers both the research and clinical applications of the new genetic therapy techniques currently being developed. The application of molecular biology has revolutionized researchers understanding of many diseases and has been readily applied for diagnostic purposes. Now-a-day this is originally conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, gene therapy now is considered for many non–life-threatening conditions, including those adversely affecting a patient’s quality of life. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. It is not very far, the justifiable optimism that with increased biotechnological improvement, gene therapy will become a standard part of clinical practice.
Antimicrobial Susceptibility, Biochemical Characterization and Molecular Typi...wilhelm mendel
Pathogenic isolates of Klebsiella pneumoniae (K. pneumoniae), particularly the extended-spectrum β-lactamase (ESBL) producing strains, are mostly associated with the failure of antibiotic therapy in nosocomial infections. The present work was designed to evaluate the impact of Mr. Trivedi’s biofield energy treatment on phenotypic and genotypic characteristics of K. pneumoniae. The strain of K. pneumoniae bearing ATCC 15380 (American Type Culture Collection) was procured from the Bangalore Genei, in sealed pack and divided into control and treated groups. Treated group was subjected to Mr. Trivedi’s biofield energy treatment and analyzed for the antimicrobial susceptibility, minimum inhibitory concentration (MIC), biochemical reactions, and biotyping using automated MicroScan Walk-Away® system. Further, the effect of biofield treatment was also evaluated using Random Amplified Polymorphic DNA (RAPD) in order to determine their epidemiological relatedness and genetic characteristics of biofield treated K. pneumoniae samples. The antimicrobial susceptibility results showed an improve sensitivity (i.e. from intermediate to susceptible) of ampicillin/sulbactam and chloramphenicol, while altered sensitivity of cephalothin (i.e. from susceptible to intermediate) was also reported as compared to the control sample. The MIC value showed two-fold decrease in MIC value of ampicillin/sulbactam (i.e. 16/8 to ≤8/4 μg/mL) and chloramphenicol (i.e. 16 to ≤ 8 μg/mL) as compared to the control. The cephalothin showed two-folds change (i.e. ≤ 8 to 16 μg/mL) in the MIC value as compared with the control. Biofield treatment showed 9.09% alterations in biochemical reactions followed by a change in biotype number (7774 4272) in the treated group with respect to the control (7774 4274). Genetic fingerprinting was performed on control and treated samples using RAPD-PCR biomarkers, which showed an average range of 11 to 15% of polymorphism among the treated samples with respect to the control. These results suggested that Mr. Trivedi’s biofield energy treatment has a significant impact on K. pneumoniae.
Phenotyping and Genotyping Characteristics of Serratia MarcescensGru Marckel
A study was performed to evaluate the impact of biofield treatment on phenotyping and genotyping characteristics of S. marcescens. Visit here for more details.
Biochemical Monitoring of Detoxifying Enzyme Levels in Field Population of Mo...BRNSS Publication Hub
The major cause of resistance mechanism in mosquitoes is the detoxification and degradation of
insecticides by overproduction of various metabolic enzymes. Quantitative metabolic enzyme assays
of carboxylesterases (α and β), mixed function oxidases (MFO), and glutathione S-transferases (GST)
have been commonly used in the detection of insecticide resistance due to its sensitive nature even at low
frequencies. For the present study, larval strains of Culex quinquefasciatus Say and Aedes aegypti (L) were
collected from the Cochin Corporation, Kerala, India, and were assayed to organophosphate temephos
and carbamate propoxur. The resistance ratio of median lethal time for temephos and propoxur from the
field population of C. quinquefasciatus and A. aegypti is higher than the laboratory population. Elevated
levels of α and β esterase enzyme were observed with the ratio of 1.6 and 1.54 for C. quinquefasciatus
and 1.51 and 1.47 for A. aegypti. In Culex mosquitoes, 1.71, and in Aedes, 1.64 fold increase in GST
enzyme level and 1.38 and 1.3 fold increase for the MFO level determined. The study results revealed
the urgent needs of improving the vector control methods by introducing alternative techniques and
strategies against mosquitoes.
An Effect of Biofield Treatment on Multidrug-resistant Burkholderia cepacia: ...Mahendra Kumar Trivedi
Aim of the present study was to analyze the impact of biofield treatment on multidrug resistant B. cepacia. Clinicalsample of B. cepacia was divided into two groups i.e. control and biofield treated.
IJERA (International journal of Engineering Research and Applications) is International online, ... peer reviewed journal. For more detail or submit your article, please visit www.ijera.com
IJERA (International journal of Engineering Research and Applications) is International online, ... peer reviewed journal. For more detail or submit your article, please visit www.ijera.com
IJERA (International journal of Engineering Research and Applications) is International online, ... peer reviewed journal. For more detail or submit your article, please visit www.ijera.com
IJERA (International journal of Engineering Research and Applications) is International online, ... peer reviewed journal. For more detail or submit your article, please visit www.ijera.com
Leprosy is a chronic infectious disease caused by
Mycobacterium leprae, discovered by Norwegian physician
in 1873.
The first known written reference to the disease was found
on Egyptian papyrus in about 1550 B.C. The disease was
well recognized in ancient China, Egypt, and India.
According to the WHO research, India continues to
record the highest number of new leprosy cases in
the world.
It currently has about 54% of all the new leprosy
cases in that 48,000 women and 13,610 children are
newly detected with leprosy
The maximum incubation period reported is as
long as 30 years
The average incubation period is between three
and ten years
Literature Survey Antibiotic ResistanceTuhin Samanta
Anti-toxin obstruction happens when microscopic organisms change in light of the utilization of these medications. Microscopic organisms, not people or creatures, become anti-toxin safe. These microorganisms may contaminate people and creatures, and the diseases they cause are more diligently to treat than those brought about by non-safe microscopic organisms.
"A Study of Clinical Profile of Leprosy in Post Leprosy Elimination Era"iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
The variants of New delhiMetallo – lactamase-1: A Comparative Assessmentinventy
Research Inventy : International Journal of Engineering and Science is published by the group of young academic and industrial researchers with 12 Issues per year. It is an online as well as print version open access journal that provides rapid publication (monthly) of articles in all areas of the subject such as: civil, mechanical, chemical, electronic and computer engineering as well as production and information technology. The Journal welcomes the submission of manuscripts that meet the general criteria of significance and scientific excellence. Papers will be published by rapid process within 20 days after acceptance and peer review process takes only 7 days. All articles published in Research Inventy will be peer-reviewed.
Apicoplast: an excellent target for antimalarial drug developmentSuman Das
Apicoplast is an organelle which is present in the apicomplexan parasites like Plasmodium species. Nowadys different drugs are developed which target different pathways present in the apicoplast.
Introduction
Disease
Important Properties
Transmission & Epidemiology
Risk factor of reactivation
Pathogenesis
Clinical Findings
Laboratory Diagnosis
Approaches to the diagnosis of latent infections
Treatment
Prevention
Microbial Biotechnology Scope, Technique and Examples in Therapeutics Zohaib HUSSAIN
Genetic engineering enables us to produce a large number of proteins in bacterial cell that were originally encoded by human genes. For example a landmark in this case is production of insulin in bacterial cell in 1982. It is first case of genetically engineered therapeutic protein used for clinical purposes. Insulin produced in this way is widely used in curing diabetes and is same in all forms as compared to original insulin
Bacterial virus (Bacteriophage).
Structure of bacteriophage.
Where we can find phage?
Families of bacteriophage.
Life cycle of bacteriophage.
Potential uses of bacteriophage.
Bacteriophage vs. antibiotics.
Factors affecting phage therapy.
Transcript: Selling digital books in 2024: Insights from industry leaders - T...BookNet Canada
The publishing industry has been selling digital audiobooks and ebooks for over a decade and has found its groove. What’s changed? What has stayed the same? Where do we go from here? Join a group of leading sales peers from across the industry for a conversation about the lessons learned since the popularization of digital books, best practices, digital book supply chain management, and more.
Link to video recording: https://bnctechforum.ca/sessions/selling-digital-books-in-2024-insights-from-industry-leaders/
Presented by BookNet Canada on May 28, 2024, with support from the Department of Canadian Heritage.
UiPath Test Automation using UiPath Test Suite series, part 3DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 3. In this session, we will cover desktop automation along with UI automation.
Topics covered:
UI automation Introduction,
UI automation Sample
Desktop automation flow
Pradeep Chinnala, Senior Consultant Automation Developer @WonderBotz and UiPath MVP
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
Essentials of Automations: Optimizing FME Workflows with ParametersSafe Software
Are you looking to streamline your workflows and boost your projects’ efficiency? Do you find yourself searching for ways to add flexibility and control over your FME workflows? If so, you’re in the right place.
Join us for an insightful dive into the world of FME parameters, a critical element in optimizing workflow efficiency. This webinar marks the beginning of our three-part “Essentials of Automation” series. This first webinar is designed to equip you with the knowledge and skills to utilize parameters effectively: enhancing the flexibility, maintainability, and user control of your FME projects.
Here’s what you’ll gain:
- Essentials of FME Parameters: Understand the pivotal role of parameters, including Reader/Writer, Transformer, User, and FME Flow categories. Discover how they are the key to unlocking automation and optimization within your workflows.
- Practical Applications in FME Form: Delve into key user parameter types including choice, connections, and file URLs. Allow users to control how a workflow runs, making your workflows more reusable. Learn to import values and deliver the best user experience for your workflows while enhancing accuracy.
- Optimization Strategies in FME Flow: Explore the creation and strategic deployment of parameters in FME Flow, including the use of deployment and geometry parameters, to maximize workflow efficiency.
- Pro Tips for Success: Gain insights on parameterizing connections and leveraging new features like Conditional Visibility for clarity and simplicity.
We’ll wrap up with a glimpse into future webinars, followed by a Q&A session to address your specific questions surrounding this topic.
Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
Search and Society: Reimagining Information Access for Radical FuturesBhaskar Mitra
The field of Information retrieval (IR) is currently undergoing a transformative shift, at least partly due to the emerging applications of generative AI to information access. In this talk, we will deliberate on the sociotechnical implications of generative AI for information access. We will argue that there is both a critical necessity and an exciting opportunity for the IR community to re-center our research agendas on societal needs while dismantling the artificial separation between the work on fairness, accountability, transparency, and ethics in IR and the rest of IR research. Instead of adopting a reactionary strategy of trying to mitigate potential social harms from emerging technologies, the community should aim to proactively set the research agenda for the kinds of systems we should build inspired by diverse explicitly stated sociotechnical imaginaries. The sociotechnical imaginaries that underpin the design and development of information access technologies needs to be explicitly articulated, and we need to develop theories of change in context of these diverse perspectives. Our guiding future imaginaries must be informed by other academic fields, such as democratic theory and critical theory, and should be co-developed with social science scholars, legal scholars, civil rights and social justice activists, and artists, among others.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
Software Delivery At the Speed of AI: Inflectra Invests In AI-Powered QualityInflectra
In this insightful webinar, Inflectra explores how artificial intelligence (AI) is transforming software development and testing. Discover how AI-powered tools are revolutionizing every stage of the software development lifecycle (SDLC), from design and prototyping to testing, deployment, and monitoring.
Learn about:
• The Future of Testing: How AI is shifting testing towards verification, analysis, and higher-level skills, while reducing repetitive tasks.
• Test Automation: How AI-powered test case generation, optimization, and self-healing tests are making testing more efficient and effective.
• Visual Testing: Explore the emerging capabilities of AI in visual testing and how it's set to revolutionize UI verification.
• Inflectra's AI Solutions: See demonstrations of Inflectra's cutting-edge AI tools like the ChatGPT plugin and Azure Open AI platform, designed to streamline your testing process.
Whether you're a developer, tester, or QA professional, this webinar will give you valuable insights into how AI is shaping the future of software delivery.
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
Speakers:
👨🏫 Andras Palfi, Senior Product Manager, UiPath
👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
Kubernetes & AI - Beauty and the Beast !?! @KCD Istanbul 2024Tobias Schneck
As AI technology is pushing into IT I was wondering myself, as an “infrastructure container kubernetes guy”, how get this fancy AI technology get managed from an infrastructure operational view? Is it possible to apply our lovely cloud native principals as well? What benefit’s both technologies could bring to each other?
Let me take this questions and provide you a short journey through existing deployment models and use cases for AI software. On practical examples, we discuss what cloud/on-premise strategy we may need for applying it to our own infrastructure to get it to work from an enterprise perspective. I want to give an overview about infrastructure requirements and technologies, what could be beneficial or limiting your AI use cases in an enterprise environment. An interactive Demo will give you some insides, what approaches I got already working for real.
State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
Sectoral targets and attacks as well as the cost of ransom
Global APT activity, AI usage, actor and tactic profiles, and implications
Rise in volumes of AI-powered cyberattacks
Major cyber events in 2024
Malware and malicious payload trends
Cyberattack types and targets
Vulnerability exploit attempts on CVEs
Attacks on counties – USA
Expansion of bot farms – how, where, and why
In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
Why are attacks on smart factories rising?
Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
State of ICS and IoT Cyber Threat Landscape Report 2024 preview
D31023033
1. Dhananjay Kumar, Anshul Sarvate, Deblina Dey, Lakshmi Sahitya U, Kumar Gaurav Shankar,
K. Kasturi / International Journal of Engineering Research and Applications
(IJERA) ISSN: 2248-9622 www.ijera.com
Vol. 3, Issue 1, January-February 2013, pp.023-033
Molecular Modeling and Simulation Studies of Acyl CoA
Synthetaseof Mycobacteriumleprae
Dhananjay Kumar*, Anshul Sarvate1, Deblina Dey1, Lakshmi Sahitya U2,
Kumar Gaurav Shankar3, K. Kasturi2
*(Department of Bioinformatics, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune, Maharashtra
1(Department of Bioinformatics, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune,
Maharashtra).
2(Department of Biotechnology, AcharyaNagarjuna University, Guntur, A. P.)
3(Department of Computer Science, JNU, India)
ABSTRACT
Leprosy or Hansen’s disease is caused by societies - leprosy was diagnosed conservatively and
an obligate intracellular pathogen i.e. thus mostly accurately18. Historically, the bulky
Mycobacterium leprae. Leprosy is a numbers of bacterium in the tissues of lepromatous
granulomatous disease of peripheral nerves and patients no doubtfulness led to the aetiologic agent.
mucosa of the upper respiratory tract. This Thus, Mycobacteriumleprae, existence suggests that
infectious disease results in Leprosy reactions it is one of the first bacterium to be determined24.In
that cause irreversible nerve damage and 1873 first convincing association of a
disabilities. The organism requires minimal set of microorganism with a hominian disease, Armauer
functional genes for its survival. Most of the Hansen27, unconcealed the leprosy bacillus in skin
genes are involved in biosynthetic and metabolic biopsies but failed to culture Mycobacteriumleprae.
pathways, so the product of these genes can be A century afterwards the nine banded armadillo33,
aimed for the novel drug target. Acyl CoA was victimized as a replacement host enabling huge
Synthetase is an enzyme that participates in fatty quantities of the bacillus which has been kept apart
acid biosynthesis. The activation of fatty acids by for biochemical and physiological studies59.
Acyl-CoA Synthetase is the need of de novo lipid Consequent efforts to corroborate procreation in
biosynthesis, fatty acid catabolism and synthetic media acquired have been equally futile,
remodeling of biological membranes. Therefore although metabolic activity can be sensed21.
by emphasizing this protein as a drug target can Leprosy is one of the oldest filmed diseases, relic a
help in the identification of novel drugs to cure serious health problem though prevalence has been
leprosy. A well organized research comprising of low extensively by 1947, as dapsone (4, 4¢-
analogue based drug design and molecular diaminodiphenylsulphone) was discovered. At that
dynamics plays a major role in obtaining the lead time it became the only effective, but exclusive
molecules. The bacteria have developed weakly bactericidal, anti-leprosy drug. The figure of
resistance against many of the drugs available in cases of leprosy worldwide remained at roughly 11
the market. Therefore identification of the novel million finished to the early-1980s but by then,
drug target and potent drug can be helpful in dapsone resistant strains of M. leprae had enlarged
better prevention of the disease. to appraising levels. The imperative comeback by
the World Health Organization to this problem was
Keywords- docking, homology modeling, leprosy, to acquire multi-drug regimens against M. leprae.
M.leprae, molecular, molecular dynamics, Since the treatment now included apace antiseptic
ramachandran plot. medicine, rifampicin and also the treatment had
good coverage, so the number of cases as expected
I Brief Introduction of Leprosy drops down71. At one stage dominance of leprosy
Leprosy was originated over 5000 years was around 3 million, though incidence (i.e. rate of
ago, almost going back to the Neolithic times50. appearance of new cases) remains as high as before
Though remaining disfiguring strip conditions were multi-drug therapy was introduced53 and
perplexed with leprosy, deformities symptomatic of immunization with BCG34,47, the incidence of
the disease now illustrious to be caused by disease remains bedevilment with more than
Mycobacterium leprae are recognizable in umpteen 690,000 new person reported annnualy72. The most
archaeological finds24. One of the most famous main usage in the leprosy check in the penultimate
example is the skull of Robert the Bruce that shows millennium has been the launching of multi-drug
the artist symptom in systemic leprosy of nasal therapy (MDT) 54 in 1982; recommendation of the
septum collapse. By gothic times, synchronous WHO study group10. Freely visible long-term multi-
archeological relic shows that - at least in few drug therapy that combines rifampicin, clofazimine
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Vol. 3, Issue 1, January-February 2013, pp.023-033
and dapsone effectively targets the bacterium patch the different drug targets we found a long-chain
minimizing the process of drug-resistant strains1. In protein (i.e. Acyl-CoA Synthetase) which is
1991 WHO starts to destroy leprosy as a public essential for fatty acid degradation, phospholipids
health problem which dramatically minimize the remodeling, and the creation of interminable Acyl-
global disease prevalence, suggesting a persistent CoA esters that regulates many physiological
unknown reservoir. In 2006, 259,017 new cases processes60,19. These membrane-bound enzymes act
were reported, out of this 54% of these new reported on non-polar hydrophobic substrates, fatty acids,
cases occurred in India, 1 of 118 countries that has generating Acyl-CoA Synthetase, primal reactive
achieved voiding status (downed as figure < 1 intermediates in lipid synthesis pathways that are
case/10,000 assemblage). Brazil, Democratic water-soluble as advantageously as powerful
Republic of the Congo, Mozambique and Nepal detergents28,65,35,66,37,75. The structure of these
acquire not achieved execution and invoice for 23% membrane proteins has not been solved for the
of new cases73. mammalian Acyl CoA Synthetase but homology to
The Rational drug use is in this overview a bacterial form, whose structure has been
incidental to the medical therapeutic view received determined, points at peculiar structural features that
at the WHO conference of 1985 in Nairobi2: are consequential for these enzymes across
Rational use of drug requires that forbearing obtain species60,28,61,4,5.
medications appropriate to their clinical needs, in In clinical studies, noteworthy advance has been
doses that grapple their own requirements, for a made concerning the immunology and
passable phase of instance and at the smallest outlay immunopathology of leprosy, the genetics of human
to them and their community44. Leprosy was resistance, mechanisms of nerve unhealthiness, and
endemic in Norway (amongst a few, stray parts of chemotherapy. In nearly all of these areas,
Europe) in Hansen's day. Later, it has become more nevertheless, leprosy remains poorly comprehended
demonstrating in tropical countries, peculiarly - but compared to different leading bacterial diseases14
not solely - in poor local societies. Of the 122 and remains a clinically cardinal disease to this day.
countries where leprosy was considered disease in
1985, 110 score now reached the end of expelling at 1.2. Causes
the state direct by 2003 and leprosy relic a The body's immune response to the
semipublic upbeat job only in 12 countries22. antigens of the leprosy bacilli may create chances of
inflammation in the skin and nerves, known as
1.1. Description of the Condition reactions. There are 2 different types of reactions:
The bacilli of leprosy are likely spread type 1 reaction or reversal reaction (RR) and type 2
through tiny droplets from the nose or mouth from reactions or erythema nodosumleprosum (ENL).
infected and raw individuals48. Tissue infected with Reactions may occur during multidrug therapy or it
the leprosy bacilli, M. leprae, contains up to 166 pg can also occur before/after the multidrug therapy
of a peculiar phenolic glycolipid for each mg dry wt. and also they are the primary cause of nerve damage
of M. Leprae51,11. Leprosy can happen in varied and impairment in leprosy67,76,38. Nerve damage
clinical forms, parasitic on the greeting of the vector occurs very slowly and oftentimes it remains
scheme. Some of the persons with a few skin unnoticed or may be it recognizes at a very late
patches and the merchandise of bacilli are relatively stage. So it shows the symptoms of a reaction which
slender; this is classified as paucibacillary (PB) forces people to seek help31,49.
leprosy48. Remaining people with many skin patches
and a superior assort of bacilli in their body and are 1.3. Impact
classified as multibacillary (MB) leprosy64,74. Leprosy is most importantly a disabling
Actually, leprosy is immunologically important 25 disease. The WHO estimates around two to three
and humans are the only famous hosts applicable to million people all over the world because of
the coefficient of leprosy; so the World Health disabilities to leprosy77. Usually people suffered
Organization (WHO) currently recommends a 6 and from leprosy, especially because of those visual
12-month handling programme for paucibacillary deformities and disabilities, dread discrimination
leprosy and multibacillary leprosy, respectively. To and stigmatization. These people may have faced
stop such kind of disease novel drug targets are intense social and also some kind of psychological
required in prescript to the organization of new problems29,55,39.
drugs against antibacterial tender pathogens.
Generally, a target should cater enough selectivity,
yielding a drug which is precise or highly selective II Target Identification
against the pathogen with respect to the human Leprosy is an unceasing bacterial disease of
host3. Moreover, the target should be intrinsic for the skin and nerves in the hands and feet and, in
growing and viability of the pathogen at least under some cases, the lining of the nose62. Leprosy can be
the stipulation of infection 45. While studying about escalating, causing eternal damage to the skin,
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Vol. 3, Issue 1, January-February 2013, pp.023-033
nerves, limbs, and eyes56. The clinical symptoms of eight 310 helices and 26 ß-strands (Fig.3a,3b). This
leprosy diversify but most of all it damages the skin, particular protein represents to the family of
nerves, and secretion membranes78. The resultant of adenylate-forming enzymes and also shows the
the muse shows that Acyl-CoA Synthetase protein presence of an A-motif (adenine-binding site;
sequence containing 579 amino acid residues with residues 300– 306) and P-motif (phosphate-
ID NO (Q9CD78) which plays a vital role in lipid binding site; residues 163–173) which forms the
metabolism58. It belongs to ATP dependent AMP- AMP/ATP binding domain, as it is demonstrated by
binding enzyme family. It activates fatty acids, Q-Site Finder41. An additional conserved region of
which functions as signaling molecules and are a 25-amino acid long segment, a fatty-acid binding
structural element of membranes6. It has one AMP region (residues 375–399; FACS signature motif),
binding domain (Fig 1)58 since, deletion and decay which is similar to the family of FACS, and
of the gene of Acyl-CoA Synthetase causes removal CASTp16 has been used to predict the given binding
of numerous grave metabolic activities12 and it can region.46
also be used as a good target to have a good control
of that disease.
III Sequence homology and Conserved
domain search
Acyl-CoA Synthetase protein describes the
evolutionary relationship with Long Chain Fatty
Acid CoA Synthetase40. It has been found that both
are homologous and further the structural properties
of Fatty Acyl CoA can be used as a reference for the
study of Acyl CoA. The Pfam65 results demonstrate
AMP-binding domain (40-491), which helps, in
catalytic commotion of the protein. This part
consists of SER/Thr/Gly colorful area and can be
analyzed again by a conserved Pro-Lys-Gly triplet.
(Fig. 1)58 the enzymes family consist of Acetyl CoA
Synthetase, luciferase and different added intimately
kindred Synthetase58.
Fig.1- showing the domain of target protein58
Pfam23 database search revealed one AMP-
binding domain. (Fig 2)46 shows multiple sequence
alignment of M.tb FadD13 with E. coli,
FadDandttLC-FACS, which reveals that there are 3
conserved regions: out of them 2 are ATP-AMP
binding domains, residues from 163– 173 are
referred as P-motif, 300–306 called as A-motif and
one fatty-acid binding domain, residues 375–399
known as FACS signature motif. These domains are
conserved within the super family of adenylate
forming enzymes. The predicted model for M. Fig.2- Multiple sequence alignment of M. tb adD13
tbFadD13consists of 2 domains—a] a large N- with E. coli fadD and ttLC-FACS. The identical
terminal domain (residues 1–395) and b] a small C- residues in the aligned sequences are indicated with
terminal domain (402–503) which are further an asterisk (*). P-motif is phosphate-binding site
connected by a six-amino acid peptide linker, i.e. the colored in blue, A-motif is adenine-binding site
L motif (residues 396– 401). Secondary structure of colored in purple, L-motif is linker motif colored in
the model was analyzed by iMolTalk15, which yellow and fatty acid binding site is indicated in
describes that the structure contains 12 α-helices, green. 46
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Vol. 3, Issue 1, January-February 2013, pp.023-033
excellent results achieved experimentally20. This
would let the users to carefully use the rapidly
generated in-silico protein models in all the contexts
where today only experimental structures provide a
solid basis: structure-based drug design, analysis of
protein function, interactions, antigenic behavior,
and rational design of proteins with increased
stability or novel functions. In adding together,
protein modeling is the merely way to obtain
structural information if any how experimental
techniques fail, sometimes due to proteins are
simply too large for NMR analysis and cannot be
crystallized for X-ray diffraction 58. For homology
modeling first the target sequence was retrieved
from the database (Table1), then BLAST-p was
performed against Protein Data Bank (PDB) and the
highest scoring entry (high bit score and low e
value) was taken as template (Table1). Finally the
protein model was generated using
modelingsoftwares(Table1).
Table-1 – The targets, templates and softwares used
for Homology Modeling46,58
Target Seque Temp Softw Reference
nce ID late are
Acyl Q9CD 1V26 Swiss SuhanyaRama
CoA 78 Mode moorthi, S.
Synthe (Swiss- ller Venkatesh
tase Prot)
Fatty CAA1 1ULT Rokk NidhiJatana et.
Acyl 6147 y-P al
CoA
4.1.SWISS-MODEL
(http://swissmodel.expasy.org) is an
automated comparative modeling server basically to
predict the three dimensional (3D) protein
structures32. SWISSMODEL provides several levels
of user interaction through its World Wide Web
interface: in the ‗first approach mode‘ only
an amino acid sequence of a protein is submitted to
build a 3D model68. Template selection, alignment
and model building are done completely automated
Fig.3-Three-dimensional model of M. tb FadD13 a) by the server. The reliability of SWISS-MODEL is
Schematic representation of M. tb FadD13. Red continuously evaluated in the EVA-CM project.
colour cylinders represent α-helix and blue arrows ROKKY-P57 a server for De novo structure
represent β-sheets. N and C terminals are prediction by the simfold energy function with the
represented in white colour.46 b) Electrostatic multi-canonical ensemble fragment assembly.
potential surface map of the protein with the A- According to the result generated from various
motif, P-motif and fatty-acid binding site. Positive protein structure evaluation servers, model 3
potentials are shown in blue, negative potentials in generated by Rokky-P was found as the best model
red, neutral in white and ligand in green.46 (Table 2)46.
IV Homology Modeling
The vital aspiration of homology modeling
is to predict a structure from its sequence with an
accuracy which will be equivalent to the most
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Vol. 3, Issue 1, January-February 2013, pp.023-033
Table No.2 - Quality assessment of the models residue in the most favoured region of
obtained by various protein structure prediction Ramachandran plot (Fig. 5)58 when it was evaluated
servers46 with a tool called Structure Analysis and
Structure PROCHECKa Verify WHAT Verification Server 47 it shows that this very structure
prediction 3Db IFc could be used as a good target model for the design
server of drug.58
Modeller 65.4% 43.06% -4.822
Prime 79.10% 89.27% -3.270
SWISS- 83.10% 93.83% -2.121
MODEL
Rokky-P- 86.60% 87.50% -0.387
Model 1
PHYRE 88.3% 87.42% -1.549
Rokky-P- 90.50% 76.59% -0.619
Model 5
Rokky-P- 90.50% 88.69% -0.143
Model 2
Rokky-P- 90.80% 86.71% -0.143
Model 4
Rokky-P- 91.50% 88.49% 0.266
Model 3
a
Percentage of residues in the most favoured region Fig.5- Shows the Ramachandran plot of the protein58
b
Percentage of residues having 3D-1D score >0.2
c
Ramchandran Z-score, Z-values above 4.0 and Ramachandran plot of the given model describes
below -4.0 are very uncommon that 99.8% of the residues lie in the allowed region
as shown in Fig. 6 with only 1 residue is available in
V Structure Visualization:- disallowed region for the same structure. The
As an ensue of Swiss-PDB Viewer, we can VERIFY-3D42 analysis is used to show the
predict the 3-dimensional structure of the protein compatibility 3D-1D score >0.2 to be 99.40%
Acyl CoA Synthetase(Fig. 4) based on the corresponding to acceptable side chain
homologous protein structure Long Chain Fatty environments. ProQ79 also gave a very good
Acid CoA Synthetase whose 3-dimensional LGScore of 6.03 and a most importantly MaxSub of
structure is already known either with the help of X- 0.17 for the model while ERRAT13 showed the
ray Crystallography or NMR. The protein contains overall quality factor to be 79.59% for the model.
the AMP binding site as template.58 The ‘what-if quality70 report’ results summarized in
(Table 3) indicate that the best sophisticated model
showed a Z-score of -2.16 which shows that it is a
suitable range for a valid structure. The Z-score of <
=-5.0 denotes a poorly refined molecule46.
Table 3- What-if quality report (Z-score) for the
initial model of FadD13 before performing the MD
simulation and for the final model of M. tb FadD13
refined by the MD simulation 46
Backb Backb Side Side Z-
one- one- chain- chain score
backb side backb -side for
one chain one chain all
contac contac conta conta conta
ts ts ct cts cts
Initi −1.25 −3.02 −2.7 −3.3 −3.3
Fig.4- Shows the predicted structure of the protein
al
Acyl-CoA Synthetase (Red – α helix, Yellow - ß
mod
Sheet) 58
el
Refi −2.24 −0.92 −1.6 −0.8 −2.1
VI Evaluation and assessment of ned
generated model:- mod
The modeled protein which is built on the el
basis of 1v26 B-Chain protein describes 83.2% of
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Vol. 3, Issue 1, January-February 2013, pp.023-033
What-if Fine packing qQualitycControlreport.
Average values of the Z-score for all contacts of the
protein can be read as follows: -5.0≤Z-score
(guaranteed wrong structure) <−3.0≤Z-score
(probably good structure) <−2.0≤Z-score (good
model)
Fig.7-Blue Colour circled Spots represents the
predicted Active Site in the target protein 58
VIII Molecular Docking
A drug named as 4 - ((4 - amino 3
chlorophenyl) sulphonyl) phenyl amine (Fig 8) has
been generated using the NCI Enhanced Server 26, as
an analogue of the first line drug, dapsone and it has
also been predicted that the drug have Anti-
Myobacterial action which could serve as the ligand.
This particular drug was also analyzed by
effectuation of Christopher Lipinski's rule-of-five69,
which confirms that the designed ligand has the
properties and structural features that make
molecules much or less like a drug.58
Fig.6 – Shows the Ramachandran plot of the final
model of the protein 46
Fig.8- Shows the generated ligand 4 - ((4 amino 3-
VII Active Site Prediction chlorophenyl) sulphonyl) phenylanmine58
Binding site was characterized by using Q-
Site Finder43 and CASTp16 and these were validated The ensue provided by Hex17 shows a quite
by using the information on binding sites in other fine docking between the ligand and the target
homologous proteins.8,30. protein and they are interpreted on the basis of
Putative Active Sites with Spheres, universally binding distance which is measured to be 5.034
known as PASS52 is used to predict the active site as Angstrom between the ligand and the active site
shown in the (Fig 7), which could be used as the (Fig 9) with respect to the Tyrosine while Dapsone
possible docking site for the newly developed shows the distance of 6.052 Angstrom with respect
ligand.58 to the same amino acid. Hence this proves that
reduction in distance between the target protein and
ligand increases the docking effect between the
target protein and its respective ligand.58
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Vol. 3, Issue 1, January-February 2013, pp.023-033
Fig.9-Showing the docked ligand to the target
protein58
Many of the substrates like ATP, CoA and
various fatty acids were docked to M. tbFadD13 by
the help of IFD (Induced Fit Docking) protocol of Fig.10- Docking of multiple ligands (ATP, fatty acid
Schrödinger63. ATP and CoA gave the best XP and CoA) to M. tbFadD13 by using induced fit
Gscore, in terms of kcal/mol. The fatty acids binded docking. A) M. tbFadD13 docked with ATP,
to M. tb FadD13 in an order of decreasing binding: lignoceric acid (24:0) and CoA with lignoceric acid
cerotic acid>lignoceric acid>palmitic acid>capric shown in pink colour, ATP in purple and CoA in
acid according to their scores. M. tb FadD13 has blue. B) Ligplot showing the protein-ligand
higher affinity for very long chain fatty acids interactions in M. tb FadD13 complexed with ATP,
especially cerotic (26:0) and lignoceric (24:0) acid lignoceric acid and CoA. ATP is represented by Atp
as compared to palmitic (16:0) / capric (10:0) acid 997, lignoceric acid by Faa 998 and CoA by Coa
as also observed through experimental studies36. 999.46
Docking had also been carried out with other
different ligands in the following order: ATP, fatty IX Molecular Dynamics
acid (lignoceric acid) followed by CoA (Fig. 10a) As the results have obtained from different
and after that the docked complex was further protein structure evaluation servers, out of them
refined using Desmond 2.29. The key amino acids model 3 generated by Rokky-P was preferred as the
interacting with the substrates were identified as: concluding model (Table 2). Desmond 2.09 was
Gly166, Lys172, Thr304, Glu305, Thr485,Lys487 forming used for the further molecular dynamics simulation
hydrogen bonds with ATP, Tyr362 and Asp371 with of the final model for a period of 12 ns. Frames
fatty acid and Thr167, Thr168 ,His170 and Tyr362 with were collected after every 1 ns, energy minimized
CoA as analyzed by LIGPLOT80(Fig. 10b).46 and after that it was evaluated with various protein-
evaluation servers. The total energy reaches
equilibrium by 10 ns as shown by the stratagem of
the total energy versus MD. After a small
rearrangement from the initial conformation, the
structure is relatively stable during the whole MD as
shown by the RMSD map analysis during the 12 ns
MD simulation (Fig 11a). Ultimately the final
model obtained was evaluated by the ProSA81
program which examines, whether the interaction of
each residue with the remainder of the protein is
maintained in a favorable manner (Figure 11b)
shows that ProSA81 of the desired model gave a Z
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Vol. 3, Issue 1, January-February 2013, pp.023-033
score within the acceptable range (-10 to 10, good
ProSA scores are negative and depend on length
of protein). Figure 11c shows that the energy
remains negative for almost all amino acid residues
indicating the acceptability of the predicted model.46
Fig.11- Analysis of the final model after molecular only chains with less than 1000 residues and a z-
dynamics simulation a) RMSD plot of the MD score ≤ 10. The z-score of M. tb FadD13 is
simulation as a function of timescale. 46 b) z-plot of highlighted as large dot c) Energy plot of the final
final model generated by ProSA. The z-plot shows model obtained by ProSA.46
X Conclusion obtained. Finally MD simulation was performed to
The protein structure of Acyl CoA refine and validate the generated model. We hope
Synthetase of Mycobacterium leprae is predicted, that the validated model of the protein presented in
this protein can be taken as drug target because it is this study will be a step forward towards the
responsible in fatty acid metabolism. Acyl CoA designing and development of novel drug targets
Synthetase shows homology with Fatty Acyl CoA against leprosy.
Synthetase of Mycobacterium tuberculosis
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