Validating Small-Molecule Force Fields for Macrocyclic Compounds Using NMR Data in Different Solvents.

ABSTRACT: Macrocycles are a promising class of compounds as therapeutics for difficult drug targets due to a favorable combination of properties: They often exhibit improved binding affinity compared to their linear counterparts due to their reduced conformational flexibility, while still being able to adapt to environments of different polarity. To assist in the rational design of macrocyclic drugs, there is need for computational methods that can accurately predict conformational ensembles of macrocycles in different environments. Molecular dynamics (MD) simulations remain one of the most accurate methods to predict ensembles quantitatively, although the accuracy is governed by the underlying force field. In this work, we benchmark four different force fields for their application to macrocycles b

SUBMITTER: Waibl F 

PROVIDER: S-EPMC11523072 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature