DFT Study of Binding Energies between Acetohydroxyacid Synthase and its Sulfonylurea Inhibitors: An Application of Quantum Pseudoreceptor Model

Abstract

The quantum mechanical interaction energy between the Acetohydroxyacid synthase (AHAS) and its sulfonylurea inhibitors were calculated with an efficient density functional theory (DFT) and a pseudoreceptor model composed of the amino acids surrounding the ligands. The results show that the calculated quantum mechanical interaction energies correlate well with experimental free energies with the correlation coefficients of 0.92 for six sulfonylurea inhibitors and the standard deviation of 0.83kcal/mol. In comparison with the force field method, the binding free energies were estimated by AutoDock 4.2 program with the correlation coefficient of 0.76 and the standard deviation of 1.40kcal/mol. It indicates that the binding between the AHAS and herbicides can be well characterized by quantum pseudoreceptor model. Based on the quantum mechanical interaction energies, some AHAS inhibitors with high binding affinity were designed by introducing a hydroxyl group at the para position of aromatic ring and on the sulfonylurea bridge respectively. AMS subject classifications: 92E10, 92C05 * Corresponding author. Email address: wangml@szu.edu.cn (M.-L. Wang) M. Chen et. al / Commun. Comput. Chem., 1 (2013), pp. 72-87 73