Improved Protein Model in SPICA Force Field

Abstract

ABSTRACTThe previous version of the SPICA coarse-grained (CG) force field (FF) protein model focused primarily on membrane proteins and successfully reproduced the dimerization free energies of several transmembrane helices and stable structures of various membrane protein assemblies. However, that model had limited accuracy when applied to other proteins, such as intrinsically disordered proteins (IDPs) and peripheral proteins, because the dimensions of the IDPs in an aqueous solution were too compact, and protein binding on the lipid membrane surface was over-stabilized. To improve the accuracy of the SPICA FF model for the simulation of such systems, in this study we introduce protein secondary structure-dependent nonbonded interaction parameters to the backbone segments and re-optimize almost all nonbonded parameters for amino acids. The improved FF proposed here successfully reproduces the radius of gyration of various IDPs, the binding sensitivity of several peripheral membrane proteins, and the dimerization free energies of several transmembrane helices. The new model also shows improved agreement with experiments on the free energy of peptide association in water. In addition, an extensive library of nonbonded interactions between proteins and lipids, including various glycerophospholipids, sphingolipids, and cholesterol, allows the study of specific interactions between lipids and peripheral and transmembrane proteins. Hence, the new SPICA FF (version 2) proposed herein is applicable with high accuracy for simulating a wide range of protein systems.Graphical abstract