Patent ID: 6341256
Filing Date: 2002-01-22
Classification: B01J,C07K,C40B,G01N,Y10S,Y10T

Abstract:
A method of determining a consensus pharmacophore for binding to a target molecule at a temperature of interest, said method comprising determining a consensus structure for each of one or more peptides or peptide derivatives having a backbone represented by rigid molecular subunits connected by bonds, the bonds allowing torsional rotation of the rigid subunit, wherein said peptides or peptide derivatives bind to said target molecule at said temperature of interest, and wherein said determining of a consensus structure employs a consensus configurational bias Monte Carlo algorithm and comprises steps of repeatedly:(a) generating proposed structures for each one of said peptides or peptide derivatives according to moves comprising constrained concerted torsional rotations about a limited region of the backbone by a method comprising (i) making a torsional angle rotation about a chosen backbone bond, and (ii) choosing subsequent backbone torsional rotations so that at least one and at most four contiguous rigid subunits of the backbone undergo a spatial displacement; and (b) accepting a proposed structure for each one of said peptides or peptide derivatives according to a configurationally-biased Metropolis acceptance probability depending on a molecular Hamiltonian further including one or more heuristic constraint terms determined from the proposed structures for each one of said peptides or peptide derivatives, until sufficient structures have been generated and accepted to permit a statistically significant determination of a consensus structure for each peptide or peptide derivative, and wherein said consensus pharmacophore comprises interatomic distances between selected chemical groups in each of said consensus structures.