Methods for calculation of kinetic isotope effects and their application to reactions catalysed by enzymes are surveyed, including consideration of cut-off approximations both old and new, empirical bond-order – bond-energy approaches, quantum-mechanical cluster methods, and hybrid quantum-mechanics/molecular mechanical methods. The unifying feature is the use of a Hessian matrix of force constants within the harmonic approximation. The merits of methods appropriate for supramolecular system, including enzymes, are discussed in contrast to commonly used methods developed for gas-phase molecules, and the importance of averaging in conformationally flexible systems is emphasised.
|Title of host publication||Simulating Enzyme Reactivity|
|Subtitle of host publication||Computational Methods in Enzyme Catalysis|
|Editors||Inaki Tunon, Vicent Moliner|
|Place of Publication||Cambridge, U. K..|
|Publisher||Royal Society of Chemistry|
|Publication status||Published - Sep 2016|