@article {49606,
	title = {Benchmarking a dual-scale hybrid simulation framework for small globular proteins combining the CHARMM36 and Martini2 models},
	journal = {Journal of Molecular Graphics \& Modelling},
	volume = {135},
	year = {2025},
	month = {MAR},
	pages = {108926},
	type = {Article},
	abstract = {<p>
	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 (3)J((HN-H alpha))-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.</p>
},
	keywords = {Hybrid simulations, Martini force-field, Mixed models, Multi-scale simulations},
	issn = {1093-3263},
	doi = {10.1016/j.jmgm.2024.108926},
	author = {Yadav, Manjul and Kharche, Shalmali and Prakash, Shikha and Sengupta, Durba}
}
