title: Fully quantum mechanical energy optimization for protein-ligand structure.
abstract: We present a quantum mechanical approach to study protein-ligand binding structure with application to a Adipocyte lipid-binding protein complexed with Propanoic Acid. The present approach employs a recently develop molecular fractionation with a conjugate caps (MFCC) method to compute protein-ligand interaction energy and performs energy optimization using the quasi-Newton method. The MFCC method enables us to compute fully quantum mechanical ab initio protein-ligand interaction energy and its gradients that are used in energy minimization. This quantum optimization approach is applied to study the Adipocyte lipid-binding protein complexed with Propanoic Acid system, a complex system consisting of a 2057-atom protein and a 10-atom ligand. The MFCC calculation is carried out at the Hartree-Fock level with a 3-21G basis set. The quantum optimized structure of this complex is in good agreement with the experimental crystal structure. The quantum energy calculation is implemented in a parallel program that dramatically speeds up the MFCC calculation for the protein-ligand system. Similarly good agreement between MFCC optimized structure and the experimental structure is also obtained for the streptavidin-biotin complex. Due to heavy computational cost, the quantum energy minimization is carried out in a six-dimensional space that corresponds to the rigid-body protein-ligand interaction.
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, Room 1001, New York, New York 10003, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiang
authors.forename: Da W
authors.initials: DW
authors.lastname: Zhang
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008962:Models, Theoretical; D011422:Propionates / Q000378:metabolism; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D011422:Propionates; D011506:Proteins; C029658:propionic acid