Chemical matter that inhabits the property-space beyond Lipinski’s ‘Rule of 5’ is a strategic investment for drug discovery pipelines across the industry. With their high molecular weight and high conformational flexibility, peptides present new and exciting challenges for computational modeling that we are embracing at Merck.<br/>Two vignettes describing the application of 2D and 3D modeling approaches to guiding the design of peptide chemical matter on the timescale of active drug discovery projects will be discussed:<br/>Firstly, a data-driven approach to computational evolution of a peptide to achieve a 100-fold permeability boost while maintaining acceptable potency.<br/>Secondly, a physics-based approach, namely REST2 advanced molecular dynamics, to prospectively guide placement of backbone changes or crosslinks to enhance or maintain potency and improve cell activity.<br/>Finally, an outlook on some of the outstanding challenges facing prospective peptide property engineering will be shared.

Modeling peptides for drug discovery

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.