SPICA Force Field for Proteins and Peptides

S Kawamoto and HH Liu and Y Miyazaki and S Seo and M Dixit and R DeVane and C MacDermaid and G Fiorin and ML Klein and W Shinoda, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 18, 3204-3217 (2022).

DOI: 10.1021/acs.jctc.1c01207

A coarse-grained (CG) model for peptides and proteins was developedas an extension of the Surface Property fItting Coarse grAined (SPICA) forcefield(FF). The model was designed to examine membrane proteins that are fullycompatible with the lipid membranes of the SPICA FF. A preliminary version of thisprotein model was created using thermodynamic properties, including the surfacetension and density in the SPICA (formerly called SDK) FF. In this study, weimproved the CG protein model to facilitate molecular dynamics (MD) simulationswith a reproduction of multiple properties from both experiments and all-atom (AA)simulations. An elastic network model was adopted to maintain the secondary structurewithin a single chain. The side-chain analogues reproduced the transfer free energyprofiles across the lipid membrane and demonstrated reasonable association freeenergy (potential of mean force) in water compared to those from AA MD. A series ofpeptides/proteins adsorbed onto or penetrated into the membrane simulated by theCG MD correctly predicted the penetration depths and tilt angles of peripheral andtransmembrane peptides/proteins as comparable to those in the orientations of proteins in membranes (OPM) database. Inaddition, the dimerization free energies of several transmembrane helices within a lipid bilayer were comparable to those fromexperimental estimation. Application studies on a series of membrane protein assemblies, scramblases, and poliovirus capsidsdemonstrated the good performance of the SPICA FF.

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