Hybrid All-Atom/Coarse-Grained Simulations of Proteins by Direct Coupling of CHARMM and PRIMO Force Fields

摘要

Hybrid all-atom/coarse-grained (AA/CG) simulations of proteins offer a computationally efficient compromise where atomistic details are only applied to biologically relevant regions while benefitting from the speedup of treating the remaining parts of a given system at the CG level. The recently developed CG model, PRIMO, allows a direct coupling with an atomistic force field with no additional modifications or coupling terms and the ability to carry out dynamic simulations without any restraints on secondary or tertiary structures. A hybrid AA/CG scheme based on combining all-atom CHARMM and coarse-grained PRIMO representations was validated via molecular dynamics and replica exchange simulations of soluble and membrane proteins. The AA/CG scheme was also tested in the calculation of the free energy profile for the transition from the closed to the open state of adenylate kinase via umbrella sampling molecular dynamics method. The overall finding is that the AA/CG scheme generates dynamics and energetics that is qualitatively and quantitatively comparable to AA simulations while offering the computational advantages of coarse-graining. This model opens the door to challenging applications where high accuracy is required only in parts of large biomolecular complexes.