The document discusses lessons learned from analyzing compounds in the ChEMBL database. It finds that vendor catalogs contain more "nasty" or reactive groups compared to compounds in ChEMBL, which are more drug-like. Analyzing author affiliations shows most ChEMBL data comes from academia, not pharmaceutical companies. Creating balanced training sets shows compounds from pharmaceutical companies are more aromatic and drug-like, while academic compounds use more decorations. The document concludes ChEMBL contains valuable implicit knowledge from pharmaceutical companies about what structural features make compounds more or less "drug-like".
Find out the latest Medical Science Liaison jobs at MSL Society Career Center. We are the only 501c3 global non-profit organization dedicated towards developing MSL profession.
Search MSL Jobs | Apply To MSL Jobs | Post MSL Jobs!
We examined predictors of Calculus II final grades within a sample of 84 college students enrolled in a hybrid course through WEPS. Predictors included “typical” psychological correlates, including math confidence, math anxiety, spatial skills and numerosity ability, as well as clickstream data from the students’ activity in the online course. Results showed the clickstream data were the best predictors of course performance, in that students who spent more time grading other students’ assignments, and students who took fewer quiz attempts, did better in the course. Math confidence and then math anxiety were the next best predictors, in that students with higher confidence and lower math anxiety performed better in the course. We will discuss how results might be dependent on the particular content of this course, and how we might use easy to collect psychological variables along with clickstream data to better understand, and potentially predict, course performance in online courses.
From newspapers to newsbrands: challenging the mythsNewsworks
Newsworks looks at some common misconceptions newsbrands face, including 'young people don't read newsbrands' and 'social media is killing newsbrands'.
My Gopeng Resort is a nature resort situated in Ulu Geruntom, 7 KM from Gopeng Town.
It is founded by Ooi Beng Yeaw, Lim Kee Siang, a group of experienced trainers, teachers, guides, & nature lovers in May 2007.
We have massive experiences in outdoor learning, adventure activities, expeditions, and team building programs and able to provide you with lifelong adventure experience!
My Gopeng Resort is famous with its activities mainly, whitewater rafting along the Sungai Kampar, and the trekking to Rafflesia flowers site, Mountain camping, biking, trekking, hiking (with Orang Asli guide to Cameron Highlands), fishing, mountain biking,river bathing, picnic, outdoor games, recreation, and more.
For lodging and facilities, we provide close to nautre comfortable stay and adequate facilities such as halls, praying room, cafeteria, and bathrooms everywhere.
For food and dining, we provide fresh and delicious food to our guests.
We are strictly a halal resort. Therefore, animals and outside food is not allowed, but you can tell us your needs and we are glad to provide you the best service as we can.
We are also a registered training provider under Pembangunan Sumber Manusia Berhad with TTT Certification.
Even we are a considerably young company; we are a very progressive company. Throughout the years of our service, we have earned many awards, certifications, and returned customers.
Challenge yourself; contact us today to find a programme that’s right for you!
Find out the latest Medical Science Liaison jobs at MSL Society Career Center. We are the only 501c3 global non-profit organization dedicated towards developing MSL profession.
Search MSL Jobs | Apply To MSL Jobs | Post MSL Jobs!
We examined predictors of Calculus II final grades within a sample of 84 college students enrolled in a hybrid course through WEPS. Predictors included “typical” psychological correlates, including math confidence, math anxiety, spatial skills and numerosity ability, as well as clickstream data from the students’ activity in the online course. Results showed the clickstream data were the best predictors of course performance, in that students who spent more time grading other students’ assignments, and students who took fewer quiz attempts, did better in the course. Math confidence and then math anxiety were the next best predictors, in that students with higher confidence and lower math anxiety performed better in the course. We will discuss how results might be dependent on the particular content of this course, and how we might use easy to collect psychological variables along with clickstream data to better understand, and potentially predict, course performance in online courses.
From newspapers to newsbrands: challenging the mythsNewsworks
Newsworks looks at some common misconceptions newsbrands face, including 'young people don't read newsbrands' and 'social media is killing newsbrands'.
My Gopeng Resort is a nature resort situated in Ulu Geruntom, 7 KM from Gopeng Town.
It is founded by Ooi Beng Yeaw, Lim Kee Siang, a group of experienced trainers, teachers, guides, & nature lovers in May 2007.
We have massive experiences in outdoor learning, adventure activities, expeditions, and team building programs and able to provide you with lifelong adventure experience!
My Gopeng Resort is famous with its activities mainly, whitewater rafting along the Sungai Kampar, and the trekking to Rafflesia flowers site, Mountain camping, biking, trekking, hiking (with Orang Asli guide to Cameron Highlands), fishing, mountain biking,river bathing, picnic, outdoor games, recreation, and more.
For lodging and facilities, we provide close to nautre comfortable stay and adequate facilities such as halls, praying room, cafeteria, and bathrooms everywhere.
For food and dining, we provide fresh and delicious food to our guests.
We are strictly a halal resort. Therefore, animals and outside food is not allowed, but you can tell us your needs and we are glad to provide you the best service as we can.
We are also a registered training provider under Pembangunan Sumber Manusia Berhad with TTT Certification.
Even we are a considerably young company; we are a very progressive company. Throughout the years of our service, we have earned many awards, certifications, and returned customers.
Challenge yourself; contact us today to find a programme that’s right for you!
The 100 acre resort is nestled in the unspoiled sylvan setting of the Nature . A short drive from Mumbai and Pune brings you to this sanctuary for the body, mind and spirit. Located amidst the breathtaking landscape of the Western Ghats, and a range of recreational options. The property also offers an inspiring backdrop for exclusive corporates, schools, collages and FIT group social gatherings.
Resort organises classes for local cuisine cooking as well as dance and pottery studios. Explore the vast surroundings of the estate on nature walks and treks though the unspoilt forest, or go mountain biking across the stunning landscape.It is a land of picturesque picnic spots, advertisement, movie shooting also popular for summer-winter camps and weekend getaway for many families Surrounding mumbai and pune.
Highlights
Exclusive setting within the serene landscape of the Western Ghats
Personalized service available
20-minute speed boat drive from Panshet/Warsgaon boating to Lavasa located nearby
Experience the thrill of dence forest with natural water fall and wild life
A range of recreational activities and excursions offered
More Details,
www.lakeweekendresort.in
Piotr Wilam - Product Development Days - Raise the bar highInnovation Nest VC
Piotr Wilam's talk at PDD 2015 in Krakow. Piotr Talks about his experience with product design from Investor POV. Check out the presentation for better overview.
I hope you find this issue to be informative and helpful in your work. Please send me any information you’d like posted in upcoming issues.
The embedded links may not work in SlideShare, so please feel free to email me for a copy at DrChrisStout@gmail.com to be added to our email list.
You can join our Facebook Group and interact with over 3300 likeminded individuals at:
https://www.facebook.com/groups/CenterForGlobalInitiatives/
Any recommendations to improve this communique would be most appreciated!
And if you’d like to support the Center’s work with a tax deductible donation, that would be fantastic(!) and do a great deal: http://centerforglobalinitiatives.org/donateNow.cfm
Cheers, and thank you for your work,
Chris
Founding Director, http://CenterForGlobalInitiatives.org
General introduction to the course followed by a basic introduction to asymmetric or stereoselective Synthesis. Then starting the course proper by looking at substrate control.
DNA and Genes Lab ActivityComplete your answers in the spaces .docxjacksnathalie
DNA and Genes Lab Activity
Complete your answers in the spaces provided. USE YOUR OWN WORDS – Yes even for definitions! Remember to add your last name and first initial to the file name prior to saving and submitting your completed assignment through Canvas.
Use your textbook, notes and these websites to answer the pre lab questions. http://learn.genetics.utah.edu/units/basics/transcribe/http://www.vcbio.science.ru.nl/en/virtuallessons/cellcycle/trans/
Pre Lab Questions:
1. What is the product of transcription?
2. What is the region of DNA called where transcription begins?
3. What is the product of translation?
4. In your own words define each of the following: Silent mutation
Missense mutation Nonsense mutation Frame shift mutation
5. Where in the cell does translation take place?
Click on the link below to access the online lab.
http://www.mhhe.com/biosci/genbio/virtual_labs_2K8/pages/DNA_And_Genes.html
Download and print the instructions for reference as you work through the lab. As you work through the lab fill in the table below. Use this information to answer the questions that follow contained in this document.
First read through the mutation guide. Once you close the guide you will see the buttons to begin the simulation. Note, you will be translating the mRNA strand into a protein.
As you work through each of the mutations fill in the charts below. You must complete 4 mutations for this lab activity. It’s good practice working with the codon table .
– Aris labs calls the codon table the ‘Genetic Code Chart’. Use the amino acid abbreviation for the protein sequence. For example the amino acid proline is abbreviated as pro.
You have to fill in all the letters AND the resulting amino acid sequence by dragging and dropping before you click the [check] button. Abrieviate STOP as either STP or END.
For each of the three mutations you will complete, fill in the table in this lab document with the original mRNA and amino acid sequence and the mRNA sequence and the resulting amino acid sequence RESULTING FROM the mutation as outlined in the mutation rule.
The various mutations represent missense, nonsense, silent and frame shift mutations. You must complete one of each. The lab will not necessarily present the mutations in this order. You must do the mutation and identify which type it is and make sure you do one of each.
6. Frame Shift Mutation example:
Provide the mutation rule you are following.
Original
A. Acids
Original
mRNA
Mutated
mRNA
Mutated
A. Acids
7. Missense Mutation example:
Provide the mutation rule you are following.
Original
A. Acids
Original
mRNA
Mutated
mRNA
Mutated
A. Acids
8. Nonsense Mutation example:
Provide the mutation rule you are following.
Original
A. Acids
Original
mRNA
Mutated
mRNA
Mutated
A. Acids
9. Silent Mutation example:
Pr ...
Exploring virtual compound space with Bayesian statisticsWillem van Hoorn
Search 10^12 virtual compounds in minutes with a Bayesian model made from 10^6 combinatorial chemistry derived compounds. This work has been published: http://pubs.acs.org/doi/abs/10.1021/ci900072g
The 100 acre resort is nestled in the unspoiled sylvan setting of the Nature . A short drive from Mumbai and Pune brings you to this sanctuary for the body, mind and spirit. Located amidst the breathtaking landscape of the Western Ghats, and a range of recreational options. The property also offers an inspiring backdrop for exclusive corporates, schools, collages and FIT group social gatherings.
Resort organises classes for local cuisine cooking as well as dance and pottery studios. Explore the vast surroundings of the estate on nature walks and treks though the unspoilt forest, or go mountain biking across the stunning landscape.It is a land of picturesque picnic spots, advertisement, movie shooting also popular for summer-winter camps and weekend getaway for many families Surrounding mumbai and pune.
Highlights
Exclusive setting within the serene landscape of the Western Ghats
Personalized service available
20-minute speed boat drive from Panshet/Warsgaon boating to Lavasa located nearby
Experience the thrill of dence forest with natural water fall and wild life
A range of recreational activities and excursions offered
More Details,
www.lakeweekendresort.in
Piotr Wilam - Product Development Days - Raise the bar highInnovation Nest VC
Piotr Wilam's talk at PDD 2015 in Krakow. Piotr Talks about his experience with product design from Investor POV. Check out the presentation for better overview.
I hope you find this issue to be informative and helpful in your work. Please send me any information you’d like posted in upcoming issues.
The embedded links may not work in SlideShare, so please feel free to email me for a copy at DrChrisStout@gmail.com to be added to our email list.
You can join our Facebook Group and interact with over 3300 likeminded individuals at:
https://www.facebook.com/groups/CenterForGlobalInitiatives/
Any recommendations to improve this communique would be most appreciated!
And if you’d like to support the Center’s work with a tax deductible donation, that would be fantastic(!) and do a great deal: http://centerforglobalinitiatives.org/donateNow.cfm
Cheers, and thank you for your work,
Chris
Founding Director, http://CenterForGlobalInitiatives.org
General introduction to the course followed by a basic introduction to asymmetric or stereoselective Synthesis. Then starting the course proper by looking at substrate control.
DNA and Genes Lab ActivityComplete your answers in the spaces .docxjacksnathalie
DNA and Genes Lab Activity
Complete your answers in the spaces provided. USE YOUR OWN WORDS – Yes even for definitions! Remember to add your last name and first initial to the file name prior to saving and submitting your completed assignment through Canvas.
Use your textbook, notes and these websites to answer the pre lab questions. http://learn.genetics.utah.edu/units/basics/transcribe/http://www.vcbio.science.ru.nl/en/virtuallessons/cellcycle/trans/
Pre Lab Questions:
1. What is the product of transcription?
2. What is the region of DNA called where transcription begins?
3. What is the product of translation?
4. In your own words define each of the following: Silent mutation
Missense mutation Nonsense mutation Frame shift mutation
5. Where in the cell does translation take place?
Click on the link below to access the online lab.
http://www.mhhe.com/biosci/genbio/virtual_labs_2K8/pages/DNA_And_Genes.html
Download and print the instructions for reference as you work through the lab. As you work through the lab fill in the table below. Use this information to answer the questions that follow contained in this document.
First read through the mutation guide. Once you close the guide you will see the buttons to begin the simulation. Note, you will be translating the mRNA strand into a protein.
As you work through each of the mutations fill in the charts below. You must complete 4 mutations for this lab activity. It’s good practice working with the codon table .
– Aris labs calls the codon table the ‘Genetic Code Chart’. Use the amino acid abbreviation for the protein sequence. For example the amino acid proline is abbreviated as pro.
You have to fill in all the letters AND the resulting amino acid sequence by dragging and dropping before you click the [check] button. Abrieviate STOP as either STP or END.
For each of the three mutations you will complete, fill in the table in this lab document with the original mRNA and amino acid sequence and the mRNA sequence and the resulting amino acid sequence RESULTING FROM the mutation as outlined in the mutation rule.
The various mutations represent missense, nonsense, silent and frame shift mutations. You must complete one of each. The lab will not necessarily present the mutations in this order. You must do the mutation and identify which type it is and make sure you do one of each.
6. Frame Shift Mutation example:
Provide the mutation rule you are following.
Original
A. Acids
Original
mRNA
Mutated
mRNA
Mutated
A. Acids
7. Missense Mutation example:
Provide the mutation rule you are following.
Original
A. Acids
Original
mRNA
Mutated
mRNA
Mutated
A. Acids
8. Nonsense Mutation example:
Provide the mutation rule you are following.
Original
A. Acids
Original
mRNA
Mutated
mRNA
Mutated
A. Acids
9. Silent Mutation example:
Pr ...
Exploring virtual compound space with Bayesian statisticsWillem van Hoorn
Search 10^12 virtual compounds in minutes with a Bayesian model made from 10^6 combinatorial chemistry derived compounds. This work has been published: http://pubs.acs.org/doi/abs/10.1021/ci900072g
Do you need help cleaning your chemistry classroom prep room? in this article an experienced high school chemistry teacher and safety enthusiast reveals simple, time saving tips to help teachers of chemistry clean and organize their prep rooms.
Embase for pharmacovigilance: Search and validation March 22 2017Ann-Marie Roche
Scientific literature plays a critical role in Pharmacovigilance and Drug Safety workflows. Monitoring literature for mentions of adverse drug reactions (ADRs) is mandated by regulatory bodies, and marketing authorization holders (MAHs) that do not properly report ADRs can be subject to heavy fines. With an increasing volume of unstructured content to cover, along with rising labor costs, MAHs are looking for ways to make their literature monitoring more effective and efficient.
Abstract and indexing (A&I) databases play an important role in Literature Monitoring – due to the vast amount of scientific literature published daily – in order for MAH’s to locate specific articles or conference presentations that may be relevant for their products (for both benefit/risk analysis and ADR detection). Rather than reading all the literature, MAH’s create search strategies that identify the relevant records in A&I databases and execute the searches regularly. GVP module VI mandates that searches are done at least weekly, but many companies maintain a daily monitoring and review cycle.
In this webinar, Senior Product Development Manager Embase, Dr. Ivan Krstic discussed best practices for saving time, staying current, validating search strategies and mitigating risk in the face of these increasingly complex processes in literature monitoring
BIO 204 Success Begins / snaptutorial.comRobinson029
What is the interdependent relationship between mitochondria and other organelles?
What are similarities and differences between the Golgi apparatus and the large central vacuole?
What is the function of chloroplast? Include functions of stroma and grana.
1. Lessons from ChEMBL Willem P. van Hoorn Senior Solutions Consultant Willem.vanhoorn@accelrys.com
2. Those who cannot remember the past are condemned to repeat it Contents
3. ‘Nasties’ Things you would not like to see in your hits Specifically: reactive/labile chemical groups Is the compound still on the plate? Activity due to (selective) non-covalent binding? Some overlap with frequent hitters/aggregators Peroxides, aldehydes, etc Not ‘structural alerts’ Off-target toxicity Toxic compounds after metabolic activation hERG binders, anilines, etc
4. This is not a new concept If you are a chemist you know many of these If you have been working in pharma you know more of these Pharma companies probably all have their in-house list of ‘forbidden/risky/ugly’ structures Some publications but no definitive public list Thus reinvention of the wheel, wasted effort
5. ChEMBL: “the most comprehensive ever seen in a public database.’” (wikipedia) “…cover a significant fraction of the SAR and discovery of modern drugs” (ChEMBL website) This must be a good source to learn what goes Experienced scientists who cared enough about compounds to measure the activity and submit the results to peer-reviewed journals ChEMBL as a teacher
6. To learn we also need to know what not to do: Compound vendor catalogues Fewer constraints on reactivity / stability Drive for diversity More customers than just pharma: Should be enriched in nasties compared to ChEMBL ChEMBL as a teacher
7. Lesson 1 ChEMBL Release 7 Dump all compounds, keep largest fragment Unique canonical smiles: 597,255 Vendor reagents Pipeline Pilot examples: Maybridge + Asinex 186,967 unique compounds Build Bayesian model ‘reagentlike’ Vendor “good” v. ChEMBL “baseline” What do reagents have in common that ChEMBL compounds don’t?
8. Training/Test: Random 80% / 20% Excellent separation ChEMBL / Reagent Reagentlike model Leave-one-out enrichment Test set enrichment
10. A look at high and low scoring compounds Colour atoms by contribution to Bayesian score Red: high contribution: reagent-like Blue: low contribution: not reagent-like Color gradient over set of molecules
14. High scoring features Low scoring features High and low scoring reagent features Seen 1029 times, of which in reagent set 1024 times Many variations of peptide bondand other polypeptide features: 635 out of 639 in reagent set
15. Learning the difference was too easy Small organic vs large polypeptide Both sets contain many series, model learns common core instead of (nasty) decorations Metric: compounds / Murcko frames ChEMBL: ~6.7, reagent: ~9.0 Number of frames / in common: ~81k / ~6k I need to resit this class Conclusions from lesson 1
16. Restrict to organic small molecules AlogP < 6, Mw < 600, organic compound filter Bayesian Model ECFP_2(smaller features compared to ECFP_6) Less likely to capture whole core Lesson 2: Rebalancing the training set
21. Less learning of “series by template” But it still happens, don’t need to capture whole ring to capture sugar, steroid, etc Some of expected nasty features found But many are not Better training set needed Series: similar in both clean/nasty training set, so that difference is not the template Many ChEMBL compounds are odd I have still not learned the lesson Conclusions from lesson 2
22. ChEMBL: What I should have started with: All compounds with IC50 or Ki expressed in nM, Against human target, Include reference: journal, volume, year, page 569,569 activities 223,896 compounds 14,383 references Lesson 3: Learning from (big) pharma
30. Creating balanced training/test sets Affiliation: Pharma, Other, Academic Keep 602 targets for which measured activities are available for all 3 affiliations Same target, same pharmacophore, some me-too work: less series learning
31. Bayesian model based on <= 2005 data Descriptors: ECFP_6 + Ro5 physical properties Categorical model: Pharma/Academic/Other
34. What makes a compound ‘Pharma’ Aromatic rings, aromatic rings, aromatic rings. IP? Absence of decorations means these are not distinctive. Number of times feature observed / how many times in academic / pharma
35. What makes a compound ‘Academic’ Aliphatic, single rings, bold usage of F and other decorations, etc. Maybe not nasty but not very druglike. Number of times feature observed / how many times in academic / pharma
38. Set out to learn nasty model, ended up with a (non)drug-like model Pharma is ‘a bit’ underrepresented 10% of MDDR is in ChEMBL (Dave Rogers) ChEMBL c/should include patent literature Over the years (big) pharma has delivered the goods and learned what does (not) work in a structure. Some of this knowledge can be extracted from ChEMBL. Ignore this at your peril Conclusions