Catalytic Site p<i>K</i>_a Values of Aspartic, Cysteine, and Serine Proteases: Constant pH MD Simulations.

ABSTRACT: Enzymatic function and activity of proteases is closely controlled by the pH value. The protonation states of titratable residues in the active site react to changes in the pH value, according to their pK_a, and thereby determine the functionality of the enzyme. Knowledge of the titration behavior of these residues is crucial for the development of drugs targeting the active site residues. However, experimental pK_a data are scarce, since the systems' size and complexity make determination of these pK_a values inherently difficult. In this study, we use single pH constant pH MD simulations as a fast and robust tool to estimate the active site pK_a values of a set of aspartic, cysteine, and serine proteases. We capture char

SUBMITTER: Hofer F 

PROVIDER: S-EPMC7312390 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature