Benchmarking a dual-scale hybrid simulation framework for small globular proteins combining the CHARMM36 and Martini2 models.

Autor: Yadav M; CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India., Kharche S; CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India. Electronic address: sa.kharche@ncl.res.in., Prakash S; CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India., Sengupta D; CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India. Electronic address: d.sengupta@ncl.res.in.
Jazyk: angličtina
Zdroj: Journal of molecular graphics & modelling [J Mol Graph Model] 2024 Dec 17; Vol. 135, pp. 108926. Date of Electronic Publication: 2024 Dec 17.
DOI: 10.1016/j.jmgm.2024.108926
Abstrakt: Multi-scale models in which varying resolutions are considered in a single molecular dynamics simulation setup are gaining importance in integrative modeling. However, combining atomistic and coarse-grain resolutions, especially for coarse-grain force fields derived from top-down approaches, have not been well explored. In this study, we have implemented and tested a dual-resolution simulation approach to model globular proteins in atomistic detail (represented by the CHARMM36 model) with the surrounding solvent in Martini2 coarse-grain detail. The hybrid scheme considered is an extension of a model implemented earlier for mainly lipid and water molecules. We have considered a set of small globular proteins and have extensively compared to atomistic benchmark simulations as well as a host of experimental observables. We show that the protein structural dynamics sampled in the hybrid scheme is robust, and the intra-protein contact maps are reproduced, despite increased fluctuations of the loop regions. A good match is observed with experimental small angle X-ray scattering (SAXS) and NMR observables, such as chemical shifts and [Formula: see text] -coupling, with the best match obtained for the chemical shifts. However, deviations are observed in the water dynamics and protein-water interactions which we attribute to the limitation of solvent screening in the coarse-grain force field. The computational speed-up achieved is about 2-3 times compared to an all-atom system. Overall, the hybrid model is able to retain the main features of the underlying atomistic conformational landscape with a two-fold speed-up in computational cost.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Durba Sengupta reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology. Durba Sengupta reports financial support was provided by India National Supercomputing mission. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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