The Use of Chemical Double‐Mutant Cycles in Biomolecular Recognition Studies: Application to HCV NS3 Protease Inhibitors

Things don′t always add up: Our understanding of biomolecular recognition processes is often complicated by the fact that the binding contributions of individual ligand–protein subcontacts do not add up in a linear fashion. Chemical double-mutant cycles are useful analyses to quantify the degree of nonadditivity in such binding phenomena, and peptidyl inhibitors of hepatitis C virus NS3 protease are used to exemplify this.