Classical molecular dynamics simulations of the D-Gln/Aquifex pyrophilus MurI and D-Glu/Aquifex pyrophilus MurI complexes have been carried out. Since the active site of the enzyme contains many charged and polar residues, several binding modes are possible. Thus, three very different stable conformations of the substrate analogue D-Gln have been found, and at least three binding modes are possible for the substrate d-Glu. These qualitative results give an explanation for the apparent disagreement between the D-Gln bound MurI X-ray crystal structure and the expected position and orientation of the substrate d-Glu in order to make it possible the assumed Cα deprotonation (by Cys70)/reprotonation (by Cys178) racemization mechanism. © 2005 American Chemical Society.