1. David Minh studies constrained molecular dynamics simulations, protein-ligand binding free energies using multiple rigid receptor structures, and Bayesian analysis of isothermal titration calorimetry data.
2. Binding free energy quantifies binding strength and can be estimated using methods like alchemical free energy calculations, molecular docking, or a new method called alchemical grid docking which uses binding potential of mean force estimates.
3. Reweighting configurations from apo protein ensemble simulations using binding potential of mean forces can reproduce holo protein ensembles, validating this new type of free energy calculation method.
Some reactions seem to obvious to fail, so what happens when they do? Quantum calculations yield invaluable insight to the nature of a reaction mechanism.
Presented at the Virtual Conference on Computational Chemistry VCCC 2014
Credit due to Guillermo Caballero on whose BSc thesis this presentation is based.
The Brønsted catalysis relationship is a Linear Free Energy Relationship (LFER) that relates ionization of an acid or base which catalyzes a reaction and the rate of the reaction.
Contributed by: Quincy Davis, Jonathan Greenhalgh, Joshua Visser (Undergraduates), University of Utah, 2016
Some reactions seem to obvious to fail, so what happens when they do? Quantum calculations yield invaluable insight to the nature of a reaction mechanism.
Presented at the Virtual Conference on Computational Chemistry VCCC 2014
Credit due to Guillermo Caballero on whose BSc thesis this presentation is based.
The Brønsted catalysis relationship is a Linear Free Energy Relationship (LFER) that relates ionization of an acid or base which catalyzes a reaction and the rate of the reaction.
Contributed by: Quincy Davis, Jonathan Greenhalgh, Joshua Visser (Undergraduates), University of Utah, 2016
DFT vibrationally averaged isotopic dipole moments of propane, propyne and wa...Antônio Arapiraca
Post Born–Oppenheimer isotopic effects and zero-point vibrational averages were previously inbodied in calculations of the dipole moments of isotopic species of some apolar molecules within the HF-SCF approximation (Arapiraca, 2011) [27]. Many other molecules, however, demand the inclusion of electronic correlation for this goal. Here, DFT calculations are reported for the isotopic effects on dipole moments of molecules with increasing permanent dipole moments, namely propane ( 0.1 debye), propyne (0.7 debye) and water (1.9 debye). The results account well for the experimental values and isotopic trends of the dipole moments of these molecules. 2014 Elsevier
Residence time distribution studies in flow through tubular electrochemical r...IJERD Editor
International Journal of Engineering Research and Development is an international premier peer reviewed open access engineering and technology journal promoting the discovery, innovation, advancement and dissemination of basic and transitional knowledge in engineering, technology and related disciplines.
International Journal of Engineering Research and Development (IJERD)IJERD Editor
journal publishing, how to publish research paper, Call For research paper, international journal, publishing a paper, IJERD, journal of science and technology, how to get a research paper published, publishing a paper, publishing of journal, publishing of research paper, reserach and review articles, IJERD Journal, How to publish your research paper, publish research paper, open access engineering journal, Engineering journal, Mathemetics journal, Physics journal, Chemistry journal, Computer Engineering, Computer Science journal, how to submit your paper, peer reviw journal, indexed journal, reserach and review articles, engineering journal, www.ijerd.com, research journals,
yahoo journals, bing journals, International Journal of Engineering Research and Development, google journals, hard copy of journal
Poster presented by K. M. Aggarwal and F. P. Keenan at 11th International Conference on Atomic Processes in Plasmas, Queen's University Belfast, 19-22 July 2011
Quantum chemical molecular dynamics simulations of graphene hydrogenationStephan Irle
Chemical adsorption of hydrogen atoms on graphite
surfaces has attracted considerable interest due to its
relevance for a broad range of areas including
plasma/fusion physics, gap tuning in graphene, and hydrogen storage. We adjusted the C-H repulsive potential of the spin-polarized self-consistent-charge density-functional tight-binding (sSCC-DFTB) method to reproduce
CCSD(T)-based relaxed potential energy curves for the
attack of atomic hydrogen on a center carbon atom of
pyrene and coronene at a tiny fraction of the computational
cost. Using this cheap quantum chemical potential, we performed direct on-the-fly Born-Oppenheimer
MD simulations while “shooting” H atoms with varying collision energies on a periodic graphene target
equilibrated at 300 Kelvin. We compared reaction cross sections for a) elastic collisions, b)
chemisorption reactions, c) penetration reactions in dependence of H/D/T kinetic energies, and found
remarkable differences to previously reported classical MD simulations of the same process. Using the
same potential, in simulations involving the shooting of up to 400 hydrogen atoms on the graphene sheet,
we observed the self-assembly of C4H, a novel polymer with localized aromatic hexagons, in agreement
with recent experimental findings.
DFT vibrationally averaged isotopic dipole moments of propane, propyne and wa...Antônio Arapiraca
Post Born–Oppenheimer isotopic effects and zero-point vibrational averages were previously inbodied in calculations of the dipole moments of isotopic species of some apolar molecules within the HF-SCF approximation (Arapiraca, 2011) [27]. Many other molecules, however, demand the inclusion of electronic correlation for this goal. Here, DFT calculations are reported for the isotopic effects on dipole moments of molecules with increasing permanent dipole moments, namely propane ( 0.1 debye), propyne (0.7 debye) and water (1.9 debye). The results account well for the experimental values and isotopic trends of the dipole moments of these molecules. 2014 Elsevier
Residence time distribution studies in flow through tubular electrochemical r...IJERD Editor
International Journal of Engineering Research and Development is an international premier peer reviewed open access engineering and technology journal promoting the discovery, innovation, advancement and dissemination of basic and transitional knowledge in engineering, technology and related disciplines.
International Journal of Engineering Research and Development (IJERD)IJERD Editor
journal publishing, how to publish research paper, Call For research paper, international journal, publishing a paper, IJERD, journal of science and technology, how to get a research paper published, publishing a paper, publishing of journal, publishing of research paper, reserach and review articles, IJERD Journal, How to publish your research paper, publish research paper, open access engineering journal, Engineering journal, Mathemetics journal, Physics journal, Chemistry journal, Computer Engineering, Computer Science journal, how to submit your paper, peer reviw journal, indexed journal, reserach and review articles, engineering journal, www.ijerd.com, research journals,
yahoo journals, bing journals, International Journal of Engineering Research and Development, google journals, hard copy of journal
Poster presented by K. M. Aggarwal and F. P. Keenan at 11th International Conference on Atomic Processes in Plasmas, Queen's University Belfast, 19-22 July 2011
Quantum chemical molecular dynamics simulations of graphene hydrogenationStephan Irle
Chemical adsorption of hydrogen atoms on graphite
surfaces has attracted considerable interest due to its
relevance for a broad range of areas including
plasma/fusion physics, gap tuning in graphene, and hydrogen storage. We adjusted the C-H repulsive potential of the spin-polarized self-consistent-charge density-functional tight-binding (sSCC-DFTB) method to reproduce
CCSD(T)-based relaxed potential energy curves for the
attack of atomic hydrogen on a center carbon atom of
pyrene and coronene at a tiny fraction of the computational
cost. Using this cheap quantum chemical potential, we performed direct on-the-fly Born-Oppenheimer
MD simulations while “shooting” H atoms with varying collision energies on a periodic graphene target
equilibrated at 300 Kelvin. We compared reaction cross sections for a) elastic collisions, b)
chemisorption reactions, c) penetration reactions in dependence of H/D/T kinetic energies, and found
remarkable differences to previously reported classical MD simulations of the same process. Using the
same potential, in simulations involving the shooting of up to 400 hydrogen atoms on the graphene sheet,
we observed the self-assembly of C4H, a novel polymer with localized aromatic hexagons, in agreement
with recent experimental findings.
LSSC2011 Optimization of intermolecular interaction potential energy paramete...Dragan Sahpaski
Optimization of intermolecular interaction potential energy parameters for Monte-Carlo and Molecular dynamics simulations using Genetic Algorithms (GA)
Nanobiosensors can be built via functionalization of atomic force microscopy (AFM) tips with
biomolecules capable of interacting with the analyte on a substrate, and the detection being
performed by measuring the force between the immobilized biomolecule and the analyte.
The optimization of such sensors may require multiple experiments to determine suitable
experimental conditions for the immobilization and detection. In this study we employ molecular
modeling techniques to assist in the design of nanobiosensors to detect herbicides. As a proof
of principle, the properties of acetyl co-enzyme A carboxylase (ACC) were obtained with
molecular dynamics simulations, from which the dimeric form in an aqueous solution was
found to be more suitable for immobilization owing to a smaller structural fluctuation than
the monomeric form. Upon solving the nonlinear Poisson–Boltzmann equation using a
finite-difference procedure, we found that the active sites of ACC exhibited a positive surface
potential while the remainder of the ACC surface was negatively charged. Therefore, optimized
biosensors should be prepared with electrostatic adsorption of ACC onto an AFM tip
functionalized with positively charged groups, leaving the active sites exposed to the analyte.
The preferential orientation for the herbicides diclofop and atrazine with the ACC active site
was determined by molecular docking calculations which displayed an inhibition coefficient
of 0.168 mM for diclofop, and 44.11 mM for atrazine. This binding selectivity for the herbicide
family of diclofop was confirmed by semiempirical PM6 quantum chemical calculations which
revealed that ACC interacts more strongly with the herbicide diclofop than with atrazine,
showing binding energies of 119.04 and +8.40 kcal mol1, respectively.
• Background and motivation – the success of pheophytin (pheo, 脫鎂葉綠素) catalyst
• Porphyrin-ring family and roles of their derivative morphologies
• Similar derivatives within DNA base pairs
• 1st-principle simulation of simplified H2 decomposition steps involving derivative DNA base pairs à energetically favorable?
• Wet DNA-catalyzed chemical battery experiment and result
• Dry DNA-catalyzed hydrogen fuel cell under room temperature
• Summary and conclusions
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
1. David Minh
1. Constrained molecular
dynamics as Gibbs sampling
2. Protein-ligand binding free energies
using multiple rigid receptor structures
3. Bayesian analysis of isothermal
titration calorimetry
2. The improvement score (%) is defined in the text. In the second and third column
1KK7 for Myosin), C = final (e.g. 1KK8 for Myosin), following Weiss and Levitt.
Rightmost two columns refer to Weiss and Levitt results.
aSpecific cases discussed in the text.
the
ing
thr
0.9
wh
(am
tra
oc
tid
mo
cee
of
P a
ste
Tek, A., Korostelev, A. A., & Flores, S. C. (2016). MMB-GUI: A fast morphing method demonstrates a possible ribosomal tRNA translocation trajectory. Nucleic Acids Research, 44(1), 95–
105. http://doi.org/10.1093/nar/gkv1457
Constrained dynamics can observe transitions
intractable with standard dynamics methods
but they are biased!
3. Tek, A., Korostelev, A. A., & Flores, S. C. (2016). MMB-GUI: A fast morphing method demonstrates a possible ribosomal tRNA translocation trajectory. Nucleic Acids Research, 44(1), 95–
105. http://doi.org/10.1093/nar/gkv1457
4. Monte Carlo moves can be constrained
dynamics simulationsGeneralized Coordinates Hamiltonian Monte Carlo
Avoids high energy a/empts
Avoids hard degrees of freedom
(GCHMC + CCHMC) leads to full configura?on space explora?on
5. CDHMC samples from the correct probability
distribution for torsion angles
0.0020
0.0025
0.0030
0.0035
⇢(↵)
NO FIXMAN
0.0020
0.0025
0.0030
0.0035
⇢(↵)
CDHMC
-180 -90 0 90 180
↵(degrees)
0.0020
0.0025
0.0030
0.0035
⇢(↵)
MIXED
6. CDHMC samples from the correct probability
distribution for coupled torsion angles
C5 PPII
C7eq
aL
C5 PPII
C7eq
aL
9. David Minh
1. Constrained molecular dynamics as
Gibbs sampling
2. Protein-ligand binding free
energies using multiple rigid
receptor structures
3. Bayesian analysis of isothermal
titration calorimetry
10. ΔG○ quantifies binding strength
CR
CL
C
free receptor concentration
free ligand concentration
complex concentration
standard state concentration (1 M)
CRL
Kd =
CRCL
CRL
dissociation constant
binding free energy G = 1
ln
✓
Kd
C
◆
RL⌦+R L
G
Kd MmMμMnMpMfM
0-4.1-8.3-12.4-16.6-20.8 kcal/mol
weak
biomolecular
lead compoundsgood drugshighest biological
affinity
biotin:streptavidin
lipitor:HMG-CoA
reductase ATP:kinase
WEAKSTRONG
benzamidine:
bovine trypsin
11. Millions Thousands
1st stage 2nd stage 3rd stage
<100
Alchemical pathways,
implicit solvent
(BEDAM/YANK)
We are developing a method with intermediate
accuracy between docking and “alchemical”
Accuracy
log(Computational Expense)
Alchemical pathways,
explicit solvent
End-point approximations
(MM/PBSA)
Molecular Docking
Alchemical Grid Dock
(AlGDock)
12. A binding potential of mean force is a binding free
energy between a flexible ligand and rigid receptor
1kzk,
from
docked pose
13. BPMFs can be averaged to get rigorous absolute ΔG○
• Rigorous
• Multiple rigid receptor structures
• Recyclable - thorough receptor sampling once, instead of
for every ligand
• Scalable - grid-based receptor-ligand interaction energies
are not dependent on receptor size
• Explains docking as an approximation
Minh, J Chem Phys 2012
G = 1
ln
⌦
e B
↵rR
R
+ G✏
B(rR) = 1
ln
⌦
e
↵rL,✏L
L,I
U(rX) = U(rX) + W(rX )
(rRL) = U(rRL) U(rR) U(rL)
Binding Free Energy
Binding PMF
Effective Potential Energy
Effective Interaction Energy
14. I. Sample configurations of the receptor
II. Estimate the binding PMF for each ligand
III. Estimate the binding free energy for each ligand
ˆB(rR) = 1
ln
1
N
NX
n=1
e (rRL,n)
Sample mean of exponential average
Only needs to be done once!
Does not need to be
reproduced for every ligand.
Helpful for systems with large
conformational change
New type of free energy
calculation
19. Reweighting the apo to holo ensemble
Apo Reweighted Apo = Holo
What we would like to do:
20. Validation of BPMF-based reweighing
• Validation approach
• Run alchemical calculations to get
apo and holo ensembles
• Calculate BPMFs for snapshots from
the apo ensemble
• Compare reweighted apo and holo
ensembles
hOiRL =
⌦
O(rR)e B(rR)
↵
R⌦
e B(rR)
↵
R
Minh, JCP 2012
21. Reweighting a 1D energy landscape
ATP
AMP
Based on 400 snapshots
25. David Minh
1. Constrained molecular dynamics as
Gibbs sampling
2. Protein-ligand binding free energies
using multiple rigid receptor structures
3. Bayesian analysis of isothermal
titration calorimetry
26. ITC experiment
The only experimental technique that measures both free
energy and enthalpy of binding.
Also allows study competitive binding, binding events in the
presence of changes in the protonation states, and in certain
cases kinetics of binding.
Measures differential power which is integrated to obtain heat.
Standard data analysis procedure is to assume a heat model
and then use nonlinear least square fitting (nonlinear
regression) to fit the heat data to the model to obtain
thermodynamic parameters.
nonlinear regression analysis
Bayesian analysis