title: Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods.
abstract: We review the first successes and failures of a "new wave" of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of "enhanced", dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects.
authors.affiliation: Institute for Theoretical Chemistry, Ulm University, Albert-Einstein-Allee 11, 89069 Ulm, Germany. duygu.yilmazer@uni-ulm.de.
authors.forename: Nusret Duygu
authors.initials: ND
authors.lastname: Yilmazer
authors.affiliation: Institute for Theoretical Chemistry, Ulm University, Albert-Einstein-Allee 11, 89069 Ulm, Germany. martin.korth@uni-ulm.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Korth
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D006860:Hydrogen Bonding; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D015203:Reproducibility of Results; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins
keywords: density functional theory; protein/ligand interactions; quantum chemistry; semi-empirical quantum mechanical methods