Patent ID: 8229721

Claim:
A method for analyzing a protein structure, the method being executed in a computer under the control of a program stored in the computer, and comprising the following steps: A) receiving, by the computer, a reference structure for a protein, whereby the said reference structure forms a representation of a three-dimensional structure of the said protein, and has a global energy E ref , the protein consists of a plurality of residue positions, each carrying a particular reference amino acid type in a specific reference conformation, and the protein residues are classified into a set of modelled residue positions and a set of conformationally fixed residues; B) substituting, by the computer, into the reference structure of step (A) a pattern, whereby the said pattern consists of one or more of the modelled residue positions defined in step (A), each carrying a particular amino acid residue type being placed at a specific residue position in the reference structure and adopting a specific conformation, and the one or more amino acid residue types of the said pattern are replacing the corresponding amino acid residue types present in the reference structure; C) optimizing, by the computer, the conformation of the reference structure of step (A) being substituted by the pattern of step (B), whereby a suitable protein structure optimization method based on a function allowing to assess the quality of a global protein structure, or any part thereof, is used in combination with a suitable conformational search method, and the said structure optimization method is applied to all modelled residue positions defined in step (A) not being located at any of the pattern residue positions defined in step (B), with the proviso that said structure optimization method is not applied to any of said pattern residue positions; D) assessing, by the computer, the energetic compatibility of the pattern defined in step (B) within the context of the reference structure defined in step (A) being structurally optimized in step (C) with respect to the said pattern, by way of comparing the global energy E(p) of the substituted and optimized protein structure with the global energy E ref of the non-substituted reference structure to obtain an energetic compatibility object energy E ECO (p); and E) generating and outputting, by the computer, to a display, a user, a readily accessible memory, another computer on a network, or another computer-readable medium, in the form of an energetic compatibility object (ECO), a value reflecting the said energetic compatibility of the pattern together with information forming a full description of the three-dimensional structure comprising the substituted pattern.