Patent ID: 8417461
Filing Date: 2013-04-09
Classification: G16B

Abstract:
1. A method of identifying a dynamically active residue that affects a catalytic reaction in a protein molecule, said method comprising: identifying a plurality of protein motions that are prevalent during a catalytic reaction mediated by a protein molecule; selecting a protein vibration mode from said plurality of protein motions based on a degree of overlap of a reaction coordinate in each of said plurality of protein motions with a reaction coordinate range of said catalytic reaction; identifying a dynamically active residue of said protein molecule by performing a computer simulation employing a computer based on said selected protein vibration modes, wherein said protein motions in said protein molecule are computed by identifying protein vibration modes coupled with said catalytic reaction, wherein quasi-harmonic analysis of conformations of said protein molecule along a reaction pathway is employed to identity said protein vibration modes, wherein degree of reactivity of said protein molecule is determined based on dynamical behavior of a reaction trajectory along a reaction pathway of said catalytic reaction, wherein said degree of reactivity is computed by identifying a change in transmission coefficient through said reaction pathway by employing a constant system energy model, wherein a total energy of a system remains constant in said constant system energy model, and wherein each velocity component of atoms in said system is scaled down by a constant factor in a computational model for said constant system energy model, and wherein a scalar that is proportional to an atomic displacement component of each atom in one of said plurality of protein vibration modes is added to each velocity component of each atom in said constant system energy model, wherein impact of said atomic displacement component on protein reactivity is identified by making the protein molecule rigid in the areas of said protein molecule by applying positional restraints proportional to atomic displacements by a factor ψ and by monitoring an impact of said positional restraints on a reaction energy barrier in said constant system energy model; and embodying, employing said computer, data representing said identified dynamically active residue of said protein molecule in a non-transitory computer readable data storage medium.