Structure-kinetic relationships that control the residence time of drug-target complexes: insights from molecular structure and dynamics.

Structure-kinetic relationships that control the residence time of drug-target complexes: insights from molecular structure and dynamics. Curr Opin Chem Biol. 2018 Jul 06;44:101-109 Authors: Lu H, Iuliano JN, Tonge PJ Abstract Time-dependent target occupancy is a function of both the thermodynamics and kinetics of drug-target interactions. However, while the optimization of thermodynamic affinity through approaches such as structure-based drug design is now relatively straight forward, less is understood about the molecular interactions that control the kinetics of drug complex formation and breakdown since this depends on both the ground and transition state energies on the binding reaction coordinate. In this opinion we highlight several recent examples that shed light on current approaches that are elucidating the factors that control the life-time of the drug-target complex. PMID: 29986213 [PubMed - as supplied by publisher]
Source: Current Opinion in Chemical Biology - Category: Biochemistry Authors: Tags: Curr Opin Chem Biol Source Type: research