ACCELERATED MOLECULAR DYNAMICS OF PROTEINS AND OTHER BIOMOLECULES

摘要

Embodiments herein relate to the field of computational biochemistry, in particular to accelerated molecular dynamics of proteins and other biomolecules. Various embodiments disclosed herein include methods, systems, and apparatus for determining the state, for example the kinetics or thermodynamics, of a biomolecule system. In some embodiments, the methods include partitioning the system's degrees of freedom into a subspace and a subspace complement according to frequency using Normal Mode Analysis (NMA), determining a harmonic approximation to the system around an initial equilibrium structure using a Mass Reweighted Hessian (MRH) of a biomolecular force field, using the partitioning to construct a damping matrix for the Langevin equation that overdamps and propagates high frequency modes using Brownian dynamics, propagating the low frequency modes using full Langevin dynamics, and accelerating the Brownian dynamics on the high frequency modes using an energy minimization. A coarse-grained normal mode analysis (CNMA) is also presented that enables application of this approach to very large proteins and long timescales.