Molecular Dynamics Study of Binding of Substrates Bearing Two Positively Charged Residues to Oligopeptidase B from Serratia proteamaculans

Abstract

The behavior of the peptide substrates GlyArgArgGly and GlyLysArgGly, which contain arginine or lysine at the Р2 position, in the active site of oligopeptidase В from the gamma-proteobacterium Serratia proteamaculans was studied by molecular dynamics simulations. The nature of the residue at the Р2 position was shown not only to influence the position of this residue and its contacts with the amino-acid environment in the substrate-binding pocket but also to affect the conformational dynamics of the entire peptide. Only the residue at the Р1 position forms persistent contacts with the S1-substrate-binding site of the enzyme, whereas contacts of the residue at the Р2 position may vary depending on its nature. Molecular dynamics simulations are shown to complement and improve the knowledge extracted from X-ray diffraction studies that enable the determination of the three-dimensional structures of molecules in one of numerous alternative conformations.