Molecular Docking Technique for Screening of Combinatorial Libraries

Molecular Docking Technique for Screening of Combinatorial Libraries Reporter: Yu Lun Kuo (D 95922037) E-mail: sscc 6991@gmail. com Date: May 31, 2007 10/19/2021 1

• Patent No. : US 7, 065, 453 • Date of Patent: Jun. 20, 2006 • Inventors: David J Diller, East Windsor, NJ (US); Kenneth M. Merz, Jr. , State College, PA (US) • Assignee: Accelrys Software, Inc. , San Diego, CA (US) 10/19/2021 2

Abstract • The molecular docking facility – Generating a binding site image of the protein – Binding site image having multiple hot spots • Matching hot spots of the binding site image to atoms in at least one solution conformation of the multiple solution conformation of the ligand – Optimizing the at least one ligand position • Allowing translation, orientation and rotatable bonds 10/19/2021 3

Background of the Invention • Protein binding site exhibit highly selective recognition of small organic molecules • Attempting the computer-aided design of therapeutic molecules – To predict and the explain the binding mode of novel chemical entities • Effective prioritization tools would allow scientists – Reducing synthesis costs 10/19/2021 4

Disclosure of the Invention • The method includes – Generating multiple solution conformations of the ligand – Generating a binding site image of the protein, the binding site image comprising multiple hot spots • Matching hot spots – Optimizing the at least one ligand position • Allowing translation, orientation and rotatable bonds of the ligand to vary 10/19/2021 5

Disclosure of the Invention • The invention comprises at least one program storage device readable by a machine – Tangibly embodying at least one program of instructions executable by the machine to perform a method of docking a ligand to a protein 10/19/2021 6

Disclosure of the Invention • For large collections – Considerable investment in both computer time and disk space • Database will typically be used many times – Disk sizes are now approaching the tera-byte level, storing the conformations for millions of compounds • Availability of parallel computers and faster CPUs 10/19/2021 7

Brief description of the Drawings 10/19/2021 8

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The Invention Claim • 1. A computer-aided method of docking a ligand to a protein so as to determine ligand conformations likely to bind to said protein • 2. At least one program storage device readable by a machine, tangibly embodying at least one program of instructions executable by the machine to perform a method of docking a ligand to a protein so as to determine ligand conformations likely to bind to said protein 10/19/2021 11

Thanks for your attention 10/19/2021 12