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

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 ( PO 3 2 - ) 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 PO 3 2 - and PO3 H- 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.