Discovery of Inhibitory Biomolecules of D-Alanine: D-Alanine Ligase of Staphylococcus aureus Using High-Throughput Virtual Screening

Kaleigh Copenhaver, Dr. Josh Beckham, Dr. Walter Fast, University of Texas at Austin, 110 Inner Campus Drive Austin, TX 78705

New antibiotic-resistant strains of Staphylococcus aureus continue to emerge, creating additional challenges to not only treating symptoms of infections but also preventing the spread of the bacteria. S. aureus is the leading cause of infections in U.S. healthcare facilities and exposure to the pathogen can lead to a variety of ailments including pneumonia, meningitis, endocarditis, bacteremia, sepsis, and in severe cases, death. D-alanine: D-alanine Ligase (DDl) is an essential enzyme of S. aureus that assists in peptidoglycan synthesis. Current antibiotics, such as Vancomycin, target and disrupt this process, but antibiotic resistance limits the use of this treatment. The objective of this research is to discover novel ligands via virtual screening that can bind and potentially inhibit DDl.  Computational ligand libraries of varying sizes and molecular scaffolds were docked against the DDl crystal structure using two virtual screening softwares, GOLD and ICM. A total of 139,091 computational ligands were virtually docked against DDl, and each ligand was given an overall binding score derived from the intermolecular forces with the protein. The ligand libraries were docked and each compound was scored and rank-ordered. Thus far, virtual screening has provided scores for positive controls between 40.29 and 71.20, negative controls between 25.80 and 64.31, and library docking scores ranging from 59.96 to 92.22. In the next phase of the project, the enzymatic activity of DDl and inhibition abilities of novel compounds will be measured through biochemical assays to determine the ligand's viability as a potential pharmaceutical. 

Additional Abstract Information

Presenter: Kaleigh Copenhaver

Institution: University of Texas at Austin

Type: Poster

Subject: Biochemistry

Status: Approved

Time and Location

Session: Poster 1
Date/Time: Mon 1:30pm-2:30pm
Session Number: 2134