title: Comparison of molecular mechanics, semi-empirical quantum mechanical, and density functional theory methods for scoring protein-ligand interactions.
abstract: Correctly ranking protein-ligand interactions with respect to overall free energy of binding is a grand challenge for virtual drug design. Here we compare the performance of various quantum chemical approaches for tackling this so-called "scoring" problem. Relying on systematically generated benchmark sets of large protein/ligand model complexes based on the PDBbind database, we show that the performance depends first of all on the general level of theory. Comparing classical molecular mechanics (MM), semiempirical quantum mechanical (SQM), and density functional theory (DFT) based methods, we find that enhanced SQM approaches perform very similar to DFT methods and substantially different from MM potentials.
authors.affiliation: Institute for Theoretical Chemistry, Ulm University, Albert-Einstein-Allee 11, 89069 Ulm, Germany.
authors.forename: Nusret Duygu
authors.initials: ND
authors.lastname: Yilmazer
authors.forename: Martin
authors.initials: M
authors.lastname: Korth
mesh_terms: D030562:Databases, Protein; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins