Predictions of Ligand Selectivity from Absolute Binding Free Energy Calculations.

ABSTRACT: Binding selectivity is a requirement for the development of a safe drug, and it is a critical property for chemical probes used in preclinical target validation. Engineering selectivity adds considerable complexity to the rational design of new drugs, as it involves the optimization of multiple binding affinities. Computationally, the prediction of binding selectivity is a challenge, and generally applicable methodologies are still not available to the computational and medicinal chemistry communities. Absolute binding free energy calculations based on alchemical pathways provide a rigorous framework for affinity predictions and could thus offer a general approach to the problem. We evaluated the performance of free energy calculations based on molecular dynamics for the prediction of sele

SUBMITTER: Aldeghi M 

PROVIDER: S-EPMC5253712 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature