Gaussian Accelerated Molecular Dynamics in OpenMM

Overview

Journal J Phys Chem B

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Jul 27

PMID 35895977

Authors

Matthew M Copeland

Hung N Do

Lane Votapka

Keya Joshi

Jinan Wang

Rommie E Amaro

Yinglong Miao

Affiliations

Soon will be listed here.

Abstract

Gaussian accelerated molecular dynamics (GaMD) is a computational technique that provides both unconstrained enhanced sampling and free energy calculations of biomolecules. Here, we present the implementation of GaMD in the OpenMM simulation package and validate it on model systems of alanine dipeptide and RNA folding. For alanine dipeptide, 30 ns GaMD production simulations reproduced free energy profiles of 1000 ns conventional molecular dynamics (cMD) simulations. In addition, GaMD simulations captured the folding pathways of three hyperstable RNA tetraloops (UUCG, GCAA, and CUUG) and binding of the rbt203 ligand to the HIV-1 Tar RNA, both of which involved critical electrostatic interactions such as hydrogen bonding and base stacking. Together with previous implementations, GaMD in OpenMM will allow for wider applications in simulations of proteins, RNA, and other biomolecules.

Citing Articles

Scrutinizing the evidence of anthracene toxicity on adrenergic receptor beta-2 and its bioremediation by fungal manganese peroxidase via in silico approaches.

Naveed M, Khatoon K, Aziz T, Naveed R, Majeed M, Din M Sci Rep. 2025; 15(1):3795.

PMID: 39885221 PMC: 11782678. DOI: 10.1038/s41598-025-85889-0.

Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8.

Sun D, Sun Y, Janezic E, Zhou T, Johnson M, Azumaya C Nat Commun. 2023; 14(1):7940.

PMID: 38040762 PMC: 10692165. DOI: 10.1038/s41467-023-43601-8.

Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling.

Carmona O, Oostenbrink C J Chem Theory Comput. 2023; 19(18):6521-6531.

PMID: 37649349 PMC: 10536968. DOI: 10.1021/acs.jctc.3c00619.

Deep Boosted Molecular Dynamics: Accelerating Molecular Simulations with Gaussian Boost Potentials Generated Using Probabilistic Bayesian Deep Neural Network.

Do H, Miao Y J Phys Chem Lett. 2023; 14(21):4970-4982.

PMID: 37219922 PMC: 10355842. DOI: 10.1021/acs.jpclett.3c00926.

Deep Boosted Molecular Dynamics (DBMD): Accelerating molecular simulations with Gaussian boost potentials generated using probabilistic Bayesian deep neural network.

Do H, Miao Y bioRxiv. 2023; .

PMID: 37034713 PMC: 10081221. DOI: 10.1101/2023.03.25.534210.

References

Celerse F, Inizan T, Lagardere L, Adjoua O, Monmarche P, Miao Y . An Efficient Gaussian-Accelerated Molecular Dynamics (GaMD) Multilevel Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems. J Chem Theory Comput. 2022; 18(2):968-977. DOI: 10.1021/acs.jctc.1c01024. View

Henzler-Wildman K, Kern D . Dynamic personalities of proteins. Nature. 2007; 450(7172):964-72. DOI: 10.1038/nature06522. View

Salomon-Ferrer R, Gotz A, Poole D, Le Grand S, Walker R . Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald. J Chem Theory Comput. 2015; 9(9):3878-88. DOI: 10.1021/ct400314y. View

Huang Y, McCammon J, Miao Y . Replica Exchange Gaussian Accelerated Molecular Dynamics: Improved Enhanced Sampling and Free Energy Calculation. J Chem Theory Comput. 2018; 14(4):1853-1864. PMC: 6747702. DOI: 10.1021/acs.jctc.7b01226. View

Ennifar E, Nikulin A, Tishchenko S, Serganov A, Nevskaya N, Garber M . The crystal structure of UUCG tetraloop. J Mol Biol. 2000; 304(1):35-42. DOI: 10.1006/jmbi.2000.4204. View

Miao Y, McCammon J . Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor. Proc Natl Acad Sci U S A. 2016; 113(43):12162-12167. PMC: 5087018. DOI: 10.1073/pnas.1614538113. View

Eastman P, Friedrichs M, Chodera J, Radmer R, Bruns C, Ku J . OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation. J Chem Theory Comput. 2013; 9(1):461-469. PMC: 3539733. DOI: 10.1021/ct300857j. View

Miao Y, Bhattarai A, Wang J . Ligand Gaussian Accelerated Molecular Dynamics (LiGaMD): Characterization of Ligand Binding Thermodynamics and Kinetics. J Chem Theory Comput. 2020; 16(9):5526-5547. PMC: 7768792. DOI: 10.1021/acs.jctc.0c00395. View

Levintov L, Paul S, Vashisth H . Reaction Coordinate and Thermodynamics of Base Flipping in RNA. J Chem Theory Comput. 2021; 17(3):1914-1921. DOI: 10.1021/acs.jctc.0c01199. View

10.

Liwo A, Czaplewski C, Oldziej S, Scheraga H . Computational techniques for efficient conformational sampling of proteins. Curr Opin Struct Biol. 2008; 18(2):134-9. PMC: 2465814. DOI: 10.1016/j.sbi.2007.12.001. View

11.

Wang J, Miao Y . Peptide Gaussian accelerated molecular dynamics (Pep-GaMD): Enhanced sampling and free energy and kinetics calculations of peptide binding. J Chem Phys. 2020; 153(15):154109. PMC: 7575327. DOI: 10.1063/5.0021399. View

12.

Lindert S, Bucher D, Eastman P, Pande V, McCammon J . Accelerated Molecular Dynamics Simulations with the AMOEBA Polarizable Force Field on Graphics Processing Units. J Chem Theory Comput. 2014; 9(11):4684-4691. PMC: 3948463. DOI: 10.1021/ct400514p. View

13.

Chen A, Garcia A . High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations. Proc Natl Acad Sci U S A. 2013; 110(42):16820-5. PMC: 3801082. DOI: 10.1073/pnas.1309392110. View

14.

Tang Z, Akhter S, Ramprasad A, Wang X, Reibarkh M, Wang J . Recognition of single-stranded nucleic acids by small-molecule splicing modulators. Nucleic Acids Res. 2021; 49(14):7870-7883. PMC: 8373063. DOI: 10.1093/nar/gkab602. View

15.

Jucker F, Heus H, Yip P, Moors E, Pardi A . A network of heterogeneous hydrogen bonds in GNRA tetraloops. J Mol Biol. 1996; 264(5):968-80. DOI: 10.1006/jmbi.1996.0690. View

16.

Do H, Wang J, Bhattarai A, Miao Y . GLOW: A Workflow Integrating Gaussian-Accelerated Molecular Dynamics and Deep Learning for Free Energy Profiling. J Chem Theory Comput. 2022; 18(3):1423-1436. PMC: 9773012. DOI: 10.1021/acs.jctc.1c01055. View

17.

Christen M, van Gunsteren W . On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A review. J Comput Chem. 2007; 29(2):157-66. DOI: 10.1002/jcc.20725. View

18.

Jucker F, Pardi A . Solution structure of the CUUG hairpin loop: a novel RNA tetraloop motif. Biochemistry. 1995; 34(44):14416-27. DOI: 10.1021/bi00044a019. View

19.

East K, Newton J, Morzan U, Narkhede Y, Acharya A, Skeens E . Allosteric Motions of the CRISPR-Cas9 HNH Nuclease Probed by NMR and Molecular Dynamics. J Am Chem Soc. 2019; 142(3):1348-1358. PMC: 7497131. DOI: 10.1021/jacs.9b10521. View

20.

Miao Y, McCammon J . Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor. Proc Natl Acad Sci U S A. 2018; 115(12):3036-3041. PMC: 5866610. DOI: 10.1073/pnas.1800756115. View