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

Hao Lu, James N Iuliano, Peter J Tonge
2018 Current Opinion in Chemical Biology  
Time-dependent target occupancy is a function of both the thermodynamics and kinetics of drugtarget 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
more » ... 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.
doi:10.1016/j.cbpa.2018.06.002 pmid:29986213 pmcid:PMC6066427 fatcat:kfs5tpwur5bqliu645da6jp7fy