title: Intermolecular Sulfur···Oxygen Interactions: Theoretical and Statistical Investigations.
abstract: Intermolecular S···O interactions are very common and are important in biological systems, but until recently, the presence of these contacts in protein-ligand systems largely depended on serendipitous discovery instead of rational design. Here we provide insight into the phenomenon of intermolecular S···O contacts by focusing on three sulfur-containing aromatic rings. Quantum mechanics is employed to characterize the strength and directionality of the S···O interactions and to determine their energy dependence on their geometric parameters. Protein Data Bank mining is performed to systematically determine the occurrence and geometry of intermolecular S···O interactions, and several representative examples are discussed. Three typical cases are investigated using a combined quantum mechanics/molecular mechanics approach to demonstrate the potential of these interactions in improving binding affinities and physiochemical properties. Overall, our work elucidates the structures and energy features of intermolecular S···O interactions and addresses their use in molecular design.
authors.affiliation: School of Basic Science, China Pharmaceutical University , No. 24 Tongjiaxiang, Nanjing 210009, P. R. China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Lead Compound Research, WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Lead Compound Research, WuXi AppTec , 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Basic Science, China Pharmaceutical University , No. 24 Tongjiaxiang, Nanjing 210009, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
mesh_terms: D062126:Databases, Chemical; D065427:Factor Xa Inhibitors / Q000737:chemistry; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory; D013455:Sulfur / Q000737:chemistry*
chemical_list: D065427:Factor Xa Inhibitors; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D011506:Proteins; D013455:Sulfur; D010100:Oxygen