Increased throughput in methods for simulating protein ligand binding and unbinding

Document Type

Review Article

Department

Paediatrics and Child Health

Abstract

By incorporating full flexibility and enabling the quantification of crucial parameters such as binding free energies and residence times, methods for investigating protein-ligand binding and unbinding via molecular dynamics provide details on the involved mechanisms at the molecular level. While these advancements hold promise for impacting drug discovery, a notable drawback persists: their relatively time-consuming nature limits throughput. Herein, we survey recent implementations which, employing a blend of enhanced sampling techniques, a clever choice of collective variables, and often machine learning, strive to enhance the efficiency of new and previously reported methods without compromising accuracy. Particularly noteworthy is the validation of these methods that was often performed on systems mirroring real-world drug discovery scenarios.

Comments

Issue and pagination are not provided by the author/publisher.

Publication (Name of Journal)

Current Opinion in Structural Biology

DOI

10.1016/j.sbi.2024.102871

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