Exact and effective pair-wise potential for protein-ligand interactions obtained from a semiempirical energy partition

Alexandre R F Carvalho; André T Puga; André Melo

doi:10.3390/ijms9091652

Exact and effective pair-wise potential for protein-ligand interactions obtained from a semiempirical energy partition

Int J Mol Sci. 2008 Sep;9(9):1652-1664. doi: 10.3390/ijms9091652. Epub 2008 Sep 2.

Authors

Alexandre R F Carvalho¹, André T Puga², André Melo¹

Affiliations

¹ REQUIMTE/Department of Chemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
² DEMEGI, Faculty of Engineering, University of Porto, Rua Dr Roberto Frias, 4200-465 Porto, Portugal.

Abstract

In this work, the partition method introduced by Carvalho and Melo was used to study the complex between Cucurbita maxima trypsin inhibitor (CMTI-I) and glycerol at the AM1 level. An effective potential, combining non-bonding and polarization plus charge transfer (PLCT) terms, was introduced to evaluate the magnitude of the interaction between each amino acid and the ligand. In this case study, the nonbonding-PLCT non-compensation characterizes the stabilization energy of the association process in study. The main residues (Gly29, Cys3 and Arg5) with net attractive effects and Arg1 (with a net repulsive effect), responsible by the stability of protein-ligand complex, are associated with large nonbonding energies non-compensated by PLCT effects. The results obtained enable us to conclude that the present decomposition scheme can be used for understanding the cohesive phenomena in proteins.

Keywords: Protein-ligand interactions; association processes; energy partition scheme; quantum partition of molecules; semiempirical methods; stabilization energy.