System and method for improved computer drug design

• US 20060041414A1
• Filed: 08/19/2005
• Published: 02/23/2006
• Est. Priority Date: 08/19/2004
• Status: Active Grant

• Current Assignee: Drug Design Methodologies LLC
• Original Assignee: Drug Design Methodologies LLC
• Inventors: Ho, Chris Meichung Wang
• Granted Patent: US 7,801,685 B2
• Time in Patent Office: Days
• US Class Current: 703/11
• CPC Class Codes: G16B 15/00 ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• CPC Class Codes: G16B 15/30 Drug targeting using structural data; Docking or binding prediction
• CPC Class Codes: G16C 20/40 Searching chemical structures or physicochemical data
• CPC Class Codes: G16C 20/50 Molecular design, e.g. of drugs

Abstract

A system and method for computer-aided drug design employs adaptive sampling and iterative fitting of mult-atomic subunits. The iterative fitting is performed by successive perturbation of the location of the multi-atomic subunits in directions that reduces potential energy.

Claims

1. A system for computer-aided drug design, the system including adaptive sampling functionality and rapid minimization functionality, the rapid minimization functionality employing iterative fitting of multi-atomic subunits by perturbing the location of the multi-atomic subunits in a real-space direction that reduces potential energy.

2. A system for computer-aided drug design, the system including iterative conformational searching having minimization functionality as an element of conformational searching iterations.

3. A method for designing drugs, the method comprising the steps of:

dividing a ligand into subunits;

for each subunit, determining force vectors by identifying steric sources of potential energy for each component atom of a subunit,

scaling the force vectors using molecular mechanics parameters to calculate a real-space direction that will minimize potential energy for the subunit;

determining the optimal six-dimensional coordinates for units using RMS fitting.

4. The method of claim 3, wherein force vectors are also determined for electrostatic sources of potential energy.

5. The method of claim 3, wherein force vectors are also determined for bond angle, bond stretching, and torsion sources of potential energy.