Starting Structure Dependence of NMR Order Parameters Derived from MD Simulations: Implications for Judging Force-Field Quality

Flap dynamics of HIV-1 protease (HIV-pr) controls the entry of inhibitors and substrates to the active site. Dynamical models from previous simulations are not all consistent with each other and not all are supported by the NMR results. In the present work, the effect of force field on the dynamics of HIV-pr is investigated by MD simulations using three AMBER force fields ff99, ff99SB, and ff03. The generalized order parameters for amide backbone are calculated from the three force fields and compared with the NMR S2 values. We found that the ff99SB and ff03 force field calculated order parameters agree reasonably well with the NMR S2 values, whereas ff99 calculated values deviate most from the NMR order parameters. Stereochemical geometry of protein models from each force field also agrees well with the remarks from NMR S2 values. However, between ff99SB and ff03, there are several differences, most notably in the loop regions. It is found that these loops are, in general, more flexible in the ff03 force field. This results in a larger active site cavity in the simulation with the ff03 force field. The effect of this difference in computer-aided drug design against flexible receptors is discussed.

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A hierarchical Bayesian framework for force field selection in molecular dynamics simulations

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2015.0032 ◽

2016 ◽

Vol 374 (2060) ◽

pp. 20150032 ◽

Cited By ~ 20

Author(s):

S. Wu ◽

P. Angelikopoulos ◽

C. Papadimitriou ◽

R. Moser ◽

P. Koumoutsakos

Keyword(s):

Experimental Data ◽

Molecular Dynamics ◽

Force Field ◽

Computational Cost ◽

Md Simulations ◽

Bayesian Framework ◽

Underlying Structure ◽

Hierarchical Bayesian ◽

Wide Range ◽

Selection Of

We present a hierarchical Bayesian framework for the selection of force fields in molecular dynamics (MD) simulations. The framework associates the variability of the optimal parameters of the MD potentials under different environmental conditions with the corresponding variability in experimental data. The high computational cost associated with the hierarchical Bayesian framework is reduced by orders of magnitude through a parallelized Transitional Markov Chain Monte Carlo method combined with the Laplace Asymptotic Approximation. The suitability of the hierarchical approach is demonstrated by performing MD simulations with prescribed parameters to obtain data for transport coefficients under different conditions, which are then used to infer and evaluate the parameters of the MD model. We demonstrate the selection of MD models based on experimental data and verify that the hierarchical model can accurately quantify the uncertainty across experiments; improve the posterior probability density function estimation of the parameters, thus, improve predictions on future experiments; identify the most plausible force field to describe the underlying structure of a given dataset. The framework and associated software are applicable to a wide range of nanoscale simulations associated with experimental data with a hierarchical structure.

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Development of a ReaxFF Force Field for Cu/S/C/H and Reactive MD Simulations of Methyl Thiolate Decomposition on Cu (100)

The Journal of Physical Chemistry B ◽

10.1021/acs.jpcb.7b06976 ◽

2017 ◽

Vol 122 (2) ◽

pp. 888-896 ◽

Cited By ~ 9

Author(s):

Jejoon Yeon ◽

Heather L. Adams ◽

Chad E. Junkermeier ◽

Adri C. T. van Duin ◽

Wilfred T. Tysoe ◽

...

Keyword(s):

Force Field ◽

Md Simulations ◽

Reaxff Force Field

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Simulating Absorption Spectra of Flavonoids in Aqueous Solution: A Polarizable QM/MM Study

Molecules ◽

10.3390/molecules25245853 ◽

2020 ◽

Vol 25 (24) ◽

pp. 5853

Author(s):

Sulejman Skoko ◽

Matteo Ambrosetti ◽

Tommaso Giovannini ◽

Chiara Cappelli

Keyword(s):

Molecular Dynamics ◽

Aqueous Solution ◽

Hydrogen Bonding ◽

Force Field ◽

Absorption Spectra ◽

Computational Study ◽

Md Simulations ◽

Quantum Mechanical ◽

Hydrogen Bonding Interactions

We present a detailed computational study of the UV/Vis spectra of four relevant flavonoids in aqueous solution, namely luteolin, kaempferol, quercetin, and myricetin. The absorption spectra are simulated by exploiting a fully polarizable quantum mechanical (QM)/molecular mechanics (MM) model, based on the fluctuating charge (FQ) force field. Such a model is coupled with configurational sampling obtained by performing classical molecular dynamics (MD) simulations. The calculated QM/FQ spectra are compared with the experiments. We show that an accurate reproduction of the UV/Vis spectra of the selected flavonoids can be obtained by appropriately taking into account the role of configurational sampling, polarization, and hydrogen bonding interactions.

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A force field for MD simulations on rhenium organometallic compounds developed from enthalpy of sublimation and X-ray diffraction measurements

The Journal of Chemical Thermodynamics ◽

10.1016/j.jct.2019.01.016 ◽

2019 ◽

Vol 133 ◽

pp. 60-69 ◽

Cited By ~ 1

Author(s):

Carlos E.S. Bernardes ◽

Mariana T. Donato ◽

M. Fátima M. Piedade ◽

Hermínio P. Diogo ◽

José N. Canongia Lopes ◽

...

Keyword(s):

Force Field ◽

Organometallic Compounds ◽

Md Simulations ◽

Enthalpy Of Sublimation ◽

X Ray Diffraction ◽

X Ray

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Starting-structure dependence of nanosecond timescale intersubstate transitions and reproducibility of MD-derived order parameters

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.24209 ◽

2012 ◽

Vol 81 (3) ◽

pp. 499-509 ◽

Cited By ~ 20

Author(s):

Tim Zeiske ◽

Kate A. Stafford ◽

Richard A. Friesner ◽

Arthur G. Palmer

Keyword(s):

Order Parameters ◽

Structure Dependence

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Force field development and simulations of senior dialkyl sulfoxides

Physical Chemistry Chemical Physics ◽

10.1039/c5cp08006a ◽

2016 ◽

Vol 18 (15) ◽

pp. 10507-10515 ◽

Cited By ~ 8

Author(s):

Vitaly V. Chaban

Keyword(s):

Molecular Dynamics ◽

Force Field ◽

Ab Initio ◽

Md Simulations ◽

Field Development ◽

Force Field Development ◽

Structure And Dynamics ◽

Ethyl Methyl ◽

Methyl Sulfoxide ◽

Diethyl Sulfoxide

Thermodynamics, structure, and dynamics of diethyl sulfoxide (DESO) and ethyl methyl sulfoxide (EMSO) were investigated using ab initio calculations and non-polarizable potential based molecular dynamics (MD) simulations.

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