How the protonation state of a phosphorylated amino acid governs molecular recognition: insights from classical molecular dynamics simulations

Abstract

Physicochemical properties of proteins are controlled mainly by post‐translational modifications such as amino acid phosphorylation. Although molecular dynamics simulations have been shown to be a valuable tool for studying the effects of phosphorylation on protein structure and dynamics, most of the previous studies assumed that the phosphate group was in the unprotonated ( PO32- ) state, even though the protonation state could in fact vary at physiological pH. In this study, we performed molecular dynamics simulations of four different protein‐phosphorylated peptide complexes both in the PO32- and PO3H− states. Our simulations delineate different dynamics and energetics between the two states, suggesting importance of the protonation state of a phosphorylated amino acid in molecular recognition.