Necessity of high-resolution for coarse-grained modeling of flexible proteins.

Abstract

The popular MARTINI coarse-grained (CG) force field requires the protein structure to be fixed, and is unsuitable for simulating dynamic processes such as protein folding. Here, we examine the feasibility of developing a flexible protein model within the MARTINI framework. The results demonstrate that the MARTINI CG scheme does not properly describe the volume and packing of protein backbone and side chains and leads to excessive collapse without structural restraints in explicit CG water. Combining atomistic protein representation with the MARTINI CG solvent, such as in the PACE model, dramatically improves description of flexible protein conformations. Yet, the CG solvent is insufficient to capture the conformational dependence of protein-solvent interactions, and PACE is unable to properly model context dependent conformational transitions. Taken together, high physical resolution at or near the atomistic level is likely necessary for flexible protein models with explicit, microscopic solvents, and the coarse-graining needs to focus on possible simplification in interaction potentials. © 2016 Wiley Periodicals, Inc.