Computational Strategy Revealing the Structural Determinant of Ligand Selectivity towards Highly Similar Protein Targets

Background: Poor selectivity of drug candidates may lead to toxicity and side effects accounting for as high as 60% failure rate, thus, the selectivity is consistently significant and challenging for drug discovery. Objective: To find highly specific small molecules towards very similar protein targets, multiple strategies are always employed, including (1) To make use of the diverse shape of binding pocket to avoid steric bump; (2) To increase...