Scaffold Hopping Transformations Using Auxiliary Restraints for Calculating Accurate Relative Binding Free Energies.

ABSTRACT: In silico screening of drug-target interactions is a key part of the drug discovery process. Changes in the drug scaffold via contraction or expansion of rings, the breaking of rings, and the introduction of cyclic structures from acyclic structures are commonly applied by medicinal chemists to improve binding affinity and enhance favorable properties of candidate compounds. These processes, commonly referred to as scaffold hopping, are challenging to model computationally. Although relative binding free energy (RBFE) calculations have shown success in predicting binding affinity changes caused by perturbing R-groups attached to a common scaffold, applications of RBFE calculations to modeling scaffold hopping are relatively limited. Scaffold hopping inevitably involves breaking and

SUBMITTER: Zou J 

PROVIDER: S-EPMC8215533 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature