EXPLORING THE INTERACTION BETWEEN D-XYLOSE ISOMERASE AND D-XYLOSE BY FREE-ENERGY CALCULATION

The numerical quadrature thermodynamic integration method is used to i nvestigate enzyme-substrate interaction of D-xylose isomerase. A scree ning function for the coulombic interaction is introduced into the sim ulation to correct the effect of finite cutoff radius for the non-bond ed interaction, The binding free energy difference for D-xylose with D -xylose isomerase and its N184D mutant has been calculated, and the re sult 3.9 +/- 1.2 kJ/mol agrees well with experimental data of 4.38 kJ/ mol. In addition, the structure and dynamics of enzyme-substrate compl ex were simulated for mutant and wild-type enzyme, respectively. Analy sis of the structures and intramolecular interactions of the complexes were found to be valuable for understanding the reaction mechanism of the enzyme D-xylose isomerase. (C) 1996 Wiley-Liss, Inc.