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.
|Number of pages||11|
|Journal||Journal of Molecular Graphics and Modelling|
|State||Published - Mar 1 2017|
Bibliographical noteFunding Information:
The computational resources for this work were provided by the Extreme Science and Engineering Discovery Environment (XSEDE) , which is supported by National Science Foundation grant number ACI-1053575. Additional computational resources for testing and data analysis were made available by the Center for Computational Sciences DLX cluster at the University of Kentucky. Acknowledgement is made to the Donors of the American Chemical Society Petroleum Research Fund for support of this research (53861-DNI4). We also thank Mingyang Sun for his technical support in graphical analysis.
© 2016 Elsevier Inc.
- Organosulfur compound
- Petroleum refining
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Computer Graphics and Computer-Aided Design
- Materials Chemistry