02478nas a2200229 4500008004100000022001400041245012900055210006900184260000800253300001100261490000800272520167100280653002301951653002401974653001701998653002802015100001802043700002202061700002002083700002002103856012502123 2025 eng d a1093-326300aBenchmarking a dual-scale hybrid simulation framework for small globular proteins combining the CHARMM36 and Martini2 models0 aBenchmarking a dualscale hybrid simulation framework for small g cMAR a1089260 v1353 a

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.

10aHybrid simulations10aMartini force-field10aMixed models10aMulti-scale simulations1 aYadav, Manjul1 aKharche, Shalmali1 aPrakash, Shikha1 aSengupta, Durba uhttps://library.ncl.res.in/content/benchmarking-dual-scale-hybrid-simulation-framework-small-globular-proteins-combining