Protonation and pK changes in protein-ligand binding.

ABSTRACT: Formation of protein-ligand complexes causes various changes in both the receptor and the ligand. This review focuses on changes in pK and protonation states of ionizable groups that accompany protein-ligand binding. Physical origins of these effects are outlined, followed by a brief overview of the computational methods to predict them and the associated corrections to receptor-ligand binding affinities. Statistical prevalence, magnitude and spatial distribution of the pK and protonation state changes in protein-ligand binding are discussed in detail, based on both experimental and theoretical studies. While there is no doubt that these changes occur, they do not occur all the time; the estimated prevalence varies, both between individual complexes and by method. The changes occur not onl

SUBMITTER: Onufriev AV 

PROVIDER: S-EPMC4437766 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature