Quantum mechanical map for protein-ligand binding with application to beta-trypsin/benzamidine complex.
We report full ab initio Hartree-Fock calculation to compute quantum mechanical interaction energies for beta-trypsin/benzamidine binding complex. In this study, the full quantum mechanical ab initio energy calculation for the entire protein complex with 3238 atoms is made possible by using a recently developed MFCC (molecular fractionation with conjugate caps) approach in which the protein molecule is decomposed into amino acid-based fragments that are properly capped. The present MFCC ab initio calculation enables us to obtain an "interaction spectrum" that provides detailed quantitative information on protein-ligand binding at the amino acid levels. These detailed information on individual residue-ligand interaction gives a quantitative molecular insight into our understanding of protein-ligand binding and provides a guidance to rational design of potential inhibitors of protein targets.
Zhang
Da W
DW
Department of Chemistry, New York University, New York, New York 10003, USA.
Xiang
Yun
Y
Gao
Ai M
AM
Zhang
John Z H
JZ
D001224:Aspartic Acid / Q000737:chemistry; D001550:Benzamidines / Q000737:chemistry*; D002627:Chemistry, Physical / Q000379:methods*; D008024:Ligands; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D011789:Quantum Theory; D014357:Trypsin / Q000737:chemistry*
D001550:Benzamidines; D008024:Ligands; D011506:Proteins; D001224:Aspartic Acid; D014357:Trypsin