Exploring the interaction between D-xylose isomerase and D-xylose by free energy calculation.

The numerical quadrature thermodynamic integration method is used to investigate enzyme-substrate interaction of D-xylose isomerase. A screening function for the coulombic interaction is introduced into the simulation to correct the effect of finite cut-off radius for the non-bonded interaction. The binding free energy difference for D-xylose with D-xylose isomerase and its N184D mutant has been calculated, and the result 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 complex were simulated for mutant and wild-type enzyme, respectively. Analysis 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.