Development of OPLS-AA/M Parameters for Simulations of G Protein-Coupled Receptors and Other Membrane Proteins

Autor:	Georgios Skiniotis, Michael Robertson
Rok vydání:	2022
Předmět:	Entropy Membrane Proteins Molecular Dynamics Simulation Physical and Theoretical Chemistry Receptors G-Protein-Coupled Computer Science Applications
Zdroj:	Journal of Chemical Theory and Computation. 18:4482-4489
ISSN:	1549-9626 1549-9618
Popis:	G protein-coupled receptors (GPCRs) and other membrane proteins are valuable drug targets, and their dynamic nature makes them attractive systems for study with molecular dynamics (MD) simulations and free energy approaches. Here, we report the development, implementation, and validation of OPLS-AA/M force field parameters to enable simulations of these systems. These efforts include the introduction of post-translational modifications including lipidations and phosphorylation. We also modify previously reported parameters for lipids to be more consistent with the OPLS-AA force field standard and extend their coverage. These new parameters are validated on a variety of test systems, with the results compared to high-level quantum mechanics calculations, experimental data, and simulations with other force fields. The results demonstrate that the new parameters reliably reproduce the behavior of membrane protein systems.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4ef14b932851b331a886c9106608f7a https://doi.org/10.1021/acs.jctc.2c00015 Zobrazit plný text záznamu