title: CHARMM force field parameters for 2'-hydroxybiphenyl-2-sulfinate, 2-hydroxybiphenyl, and related analogs.
abstract: 2'-Hydroxybiphenyl-2-sulfinate (HBPS) desulfinase (DszB) catalyzes the cleavage of the carbon-sulfur bond from HBPS in the final step of microbial 4S pathway desulfurization reactions. DszB is notable for its substrate specificity and exhibits product inhibition, both of which hinder the overall 4S pathway turnover rate. To understand the molecular-level contributions to substrate and inhibitor binding to DszB, we plan to perform molecular dynamic simulations bound to an array of naphthenic molecules and biphenyl analogues of HBPS. However, many of the small molecules we are interested in are not included in standard force field packages, and thus, we must first produce accurate molecular mechanics force fields. Here, we develop and validate CHARMM-compatible force field parameters for the HBPS substrate, the 2-hydroxybiphenyl product, and potential inhibitors including: 2,2'-biphenol, 2-biphenyl carboxylic acid, 1,8-naphthosultam, and 1,8-naphthosultone. The selected molecules represent biphenyl compounds having both a single and double functional group and the planar naphthenic molecule class, all likely present in the oil-rich environment surrounding DszB-producing microorganisms. The Force Field Toolkit (ffTK) in VMD was used to optimize charge, bond distance, angle, and dihedral parameters. Optimized geometries were determined from quantum mechanical calculations. Molecular simulations of the molecules in explicit and implicit water solutions were conducted to assess the abilities of optimized parameters to recapitulate optimized geometries. Calculated infrared (IR) spectra were obtained and compared with experimental IR spectra for validation of the optimized MM parameters.
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, 177 F. Paul Anderson Tower, Lexington, KY 40506, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, 177 F. Paul Anderson Tower, Lexington, KY 40506, USA.
authors.forename: Ishan A
authors.initials: IA
authors.lastname: Fursule
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, 177 F. Paul Anderson Tower, Lexington, KY 40506, USA.
authors.forename: Landon C
authors.initials: LC
authors.lastname: Mills
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, 4810 Alben Barkley Drive, Paducah, KY 42002, USA.
authors.forename: Derek L
authors.initials: DL
authors.lastname: Englert
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, 177 F. Paul Anderson Tower, Lexington, KY 40506, USA.
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Berron
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, 177 F. Paul Anderson Tower, Lexington, KY 40506, USA. Electronic address: christy.payne@uky.edu.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Payne
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D013055:Spectrophotometry, Infrared; D013452:Sulfonium Compounds / Q000737:chemistry*; D054159:Torsion, Mechanical
chemical_list: D001713:Biphenyl Compounds; D013452:Sulfonium Compounds; C004369:2-phenylphenol
keywords: Biodesulfurization; Dibenzothiophene; Organosulfur compound; Parameterization; Petroleum refining