Transition-state structural refinement with GRACE and CHARMM: realistic modelling of lactate dehydrogenase using a combined quantum/classical method

A transition structure for reduction of pyruvate catalysed by lactate dehydrogenase is refined and characterised in hybrid quantum mechanical/molecular mechanical (AM1/CHARMM) calculations involving a fully flexible active-site region by means of a novel procedure (GRACE), and is remarkably similar to that calculated in vacuo.