Patent ID: 6185548
Filing Date: 2001-02-06
Classification: G16B,G16H,Y10S

Abstract:
A method for determining the free energy of binding of a potential ligand to a receptor, comprising the steps of:obtaining a structure and a free energy of binding to said receptor for each of two or more actual receptor ligands;orienting said structures of said two or more actual receptor ligands for maximum geometric coincidence with each other;determining an electrostatic potential at each of more than one point on a van der Waals surface of each of said actual receptor ligands;thereafter, mapping each of said electrostatic potentials of each of said actual receptor ligands onto a geometric surface of one of said two or more actual receptor ligands, each of said two or more actual receptor ligands being thereby described by an identical surface geometry but a different electrostatic potential surface, and each of said electrostatic potentials being described by positional information relating said electrostatic potentials to said geometric surface;thereafter, inputting said electrostatic potentials, said positional information, and said free energy of binding of one of said two or more actual receptor ligands into a neural network;thereafter, training said neural network until said neural network predicts said free energy of binding of said one of said two or more actual receptor ligands;repeating said steps of inputting and training for each of the remaining said two or more actual receptor ligands to produce a trained network;thereafter, determining a potential ligand electrostatic potential at each of more than one point on a van der Waals surface of said potential ligand, said potential ligand having a known structure and an unknown free energy of binding to said receptor;orienting said structure of said potential ligand for maximum geometric coincidence with said structures of said two or more actual receptor ligands;thereafter, mapping each of said electrostatic potentials of said potential ligand onto a geometric surface of one of said two or more actual receptor ligands, said potential ligand having a surface geometry identical to that of said two or more actual receptor ligands, but a different electrostatic potential surface, and each of said electrostatic potentials of said potential ligand being described by positional information relating said electrostatic potentials to said geometric surface;thereafter, inputting said electrostatic potentials and said positional information of said electrostatic potentials of said potential ligand into said trained network; andusing said trained network to calculate a free energy of binding of said potential ligand to said receptor.