Date Available
1-28-2018
Year of Publication
2018
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Engineering
Department/School/Program
Chemical and Materials Engineering
First Advisor
Dr. Christina M. Payne
Second Advisor
Dr. Barbara L. Knutson
Abstract
The biodesulfurization 4S-pathway is a promising complementary enzymatic approach to remove sulfur from recalcitrant thiophenic derivatives in petroleum products that remain from conventional hydrodesulfurization method without diminishing the calorific value of oil. The final step of this pathway involves the carbon-sulfur bond cleavage from HBPS, and the production of the final products 2-hydroxybiphenyl (HBP) and sulfite, has been recognized as the rate-limiting step, partially as a result of product inhibition. However, the mechanisms and factors responsible for product inhibition in the last step have not been fully understood. In this work, we proposed a computational investigation using molecular dynamic simulations and free energy calculations on 2’-hydroxybiphenyl-2-sulfinate (HBPS) desulfinase (DszB) with different bound ligands as well as different solvent conditions to develop a fundamental understanding of the molecular-level mechanism responsible for product inhibition. Based on available crystal structures of DszB and biochemical characterization, we proposed a “gate” area close to substrate binding site of DszB is responsible for ligand egress and plays a role in product inhibition. We have conducted biphasic molecular dynamic simulations to evaluate the proposed gate area functionality. Non-bonded interaction energy analysis shows that hydrophobic residues around the gate area produce van der Waals interactions inhibiting translocation through the gate channel, and therefore, the molecules are easily trapped inside the binding site. Umbrella sampling molecular dynamics was performed to obtain the energy penalty associated with gate conformational change from open to close, which was 2.4 kcal/mol independent of solvent conditions as well as bound ligands. Free energy perturbation calculations were conducted for a group of six selected molecules bound to DszB. The selections were based on functional group representation and to calculate binding free energies that were directly comparable to experimental inhibition constants, KI. Our work provides a fundamental molecular-level analysis on product inhibition for the biodesulfurization 4S-pathway.
Digital Object Identifier (DOI)
https://doi.org/10.13023/ETD.2018.024
Recommended Citation
Yu, Yue, "UNDERSTANDING INHIBITION OF A BIODESULFURIZATION ENZYME TO IMPROVE SULFUR REMOVAL FROM PETROLEUM" (2018). Theses and Dissertations--Chemical and Materials Engineering. 81.
https://uknowledge.uky.edu/cme_etds/81
Included in
Biochemical and Biomolecular Engineering Commons, Petroleum Engineering Commons, Thermodynamics Commons