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

Do, Hung N.Miao, Yinglong2023-08-162023-08-162023-05-23Do, H. N., & Miao, Y. (2023). Deep Boosted Molecular Dynamics: Accelerating Molecular Simulations with Gaussian Boost Potentials Generated Using Probabilistic Bayesian Deep Neural Network. The journal of physical chemistry letters, 14(21), 4970–4982. https://doi.org/10.1021/acs.jpclett.3c00926https://hdl.handle.net/1808/34748This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry Letters, copyright Copyright © 2023 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jpclett.3c00926.We have developed a new deep boosted molecular dynamics (DBMD) method. Probabilistic Bayesian neural network models were implemented to construct boost potentials that exhibit Gaussian distribution with minimized anharmonicity, thereby allowing for accurate energetic reweighting and enhanced sampling of molecular simulations. DBMD was demonstrated on model systems of alanine dipeptide and the fast-folding protein and RNA structures. For alanine dipeptide, 30 ns DBMD simulations captured up to 83–125 times more backbone dihedral transitions than 1 μs conventional molecular dynamics (cMD) simulations and were able to accurately reproduce the original free energy profiles. Moreover, DBMD sampled multiple folding and unfolding events within 300 ns simulations of the chignolin model protein and identified low-energy conformational states comparable to previous simulation findings. Finally, DBMD captured a general folding pathway of three hairpin RNAs with the GCAA, GAAA, and UUCG tetraloops. Based on a deep learning neural network, DBMD provides a powerful and generally applicable approach to boosting biomolecular simulations. DBMD is available with open source in OpenMM at https://github.com/MiaoLab20/DBMD/.Copyright © 2023 American Chemical SocietyProbabilistic neural networksMolecular dynamicsProtein foldingRNA foldingFree energy profilesDeep Boosted Molecular Dynamics: Accelerating Molecular Simulations with Gaussian Boost Potentials Generated Using Probabilistic Bayesian Deep Neural NetworkArticle10.1021/acs.jpclett.3c00926https://orcid.org/0000-0002-6497-4096https://orcid.org/0000-0003-3714-1395PMC10355842embargoedAccess