Protein-Ligand Binding Affinity Directed Multi-Objective Drug Design Based on Fragment Representation Methods

Drug discovery is a challenging process with a vast molecular space to be explored and numerous pharmacological properties to be appropriately considered. Among various drug design protocols, fragment-based drug design is an effective way of constraining the search space and better utilizing biologically active compounds. Motivated by fragment-based drug search for a given protein target and the emergence of artificial intelligence (AI) approaches in this field, this work advances the field of in silico drug design by (1) integrating a graph fragmentation-based deep generative model with a deep evolutionary learning process for large-scale multi-objective molecular optimization, and (2) applying protein-ligand binding affinity scores together with other desired physicochemical properties as objectives. Our experiments show that the proposed method can generate novel molecules with improved property values and binding affinities.

Name thesis:degree_name

M.Sc. Computer Science

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Faculty of Mathematics and Science

Department dc:contributor.department

Department of Computer Science

Grantor

Brock University

Year dc:date.issued

2023

Author dc:creator

• Mukaidaisi, Muhetaer

• drug design
• multi-objective optimization
• deep evolutionary learning
• graph fragmentation
• protein-ligand binding affinity

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10464/17426

OAI identifier oai:identifier

oai:brocku.scholaris.ca:10464/17426