Efficient determination of protein-protein standard binding free energies from first principles.

ABSTRACT: Characterizing protein-protein association quantitatively has been a longstanding challenge for computer simulations. Here, a theoretical framework is put forth that addresses this challenge on the basis of detailed all-atom molecular dynamics simulations with explicit solvent. The proposed methodology relies upon independent potential of mean force (PMF) free-energy calculations carried out sequentially, wherein the biological objects are restrained in the conformation, position and orientation of the bound state, using adequately chosen biasing potentials. These restraints systematically narrow down the configurational entropy available to the system and effectively guarantee that the relevant network of interactions is properly sampled as the two proteins reversibly associate. Decomposi

SUBMITTER: Gumbart JC 

PROVIDER: S-EPMC3809040 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature