Patent ID: 7983887

Claim:
A computer-based method for generating a model for a protein structure from a primary amino acid sequence of a protein comprising: providing a computer including a memory that is coupled to a processor, wherein said computer is configured to execute computer-executable program instructions including the steps of: a) defining an extended conformation from the primary amino acid sequence of the protein; b) relaxing the extended conformation; c) performing conformational sampling through molecular dynamics simulation on the relaxed extended conformation; d) computing an average structure (R avg ) and protein vibrational modes (ω) based on the conformations sampled in step (c); e) determining two new protein conformations, R + and R − , for each protein vibrational mode by displacing R avg along ω by a factor of η in positive and negative displacement directions respectively; f) searching for local energy minima by performing energy minimization on R + and R − and selecting each new conformation with lowest energy; g) repeating steps (c) through (f) one or more times to produce one or more low energy conformations; h) selecting the lowest energy conformation from step (g); i) after performing step (h), performing conformational sampling through molecular dynamics simulation on a latest selected lowest energy conformation; j) computing an average structure (R avg ) and protein vibrational modes (ω) based on the conformations sampled in step (i); k) adding kinetic energy to a protein vibrational mode (ω) by scaling atomic velocities by a multiplication factor of f having a value selected from a range from 1 to 1,000 to produce a new configuration, wherein said atomic velocities are scaled in proportion to atomic displacements indicated by said protein vibration mode (ω) by multiplying said multiplication factor off to each of said atomic velocities; l) searching for local energy minima by performing a molecular dynamics simulation on the new configuration determined in (k) and selecting a configuration with lowest energy among configurations generated by said molecular dynamics simulation; m) optionally repeating steps (i) through (l) for one or more times; n) repeating steps (c) through (m) until a native state of the protein is determined; and o) generating a molecular model of the protein at said native state; causing said computer to generate said molecular model by providing the primary amino acid sequence of the protein to said computer; and outputting, in a non-transitory tangible medium, a manifestation of said molecular model generated by said computer in a form capable of direct human perception.