Application of Fragment Molecular Orbital Calculations to Functional Analysis of Enzymes

Abstract

Enzymes are biocatalysts catalyzing various reactions in metabolism. Several of amino acid metabolizing enzymes are applied to industrial usage because of their high functionalities, such as high specificity and reactivity. Elucidation of reaction mechanism of these enzymes would be helpful to improve their functions. In this chapter, we introduce how combinational analysis of fragment molecular orbital (FMO) calculation, structural, and biochemical analysis can elucidate molecular mechanism of industrially important enzymes. Firstly, we will represent that the combinational analysis can represent why artificially designed R-selective amine oxidase reacts with R-methylbenzylamine (R-MBA) in racemic MBA selectively without being inhibited by S-MBA. Secondly, for the highly selective L-threonine 3-dehydrogenase (TDH) which is applied to quantify L-threonine concentration in various samples, we will show that FMO calculation can suggest existence of residue working as a sensor to detect completion of enzyme reaction in TDH. In the future, many more enzymatic functions and protein mechanics will be elucidated by combinatorial approaches based on computational chemistry, structural biology, and enzyme chemistry.