30th Annual Student Research Conference
Computational Analysis of NS2B-NS3 Zika Protease Inhibition
Megan E. Kilian
Dr. Bill R. Miller, Faculty Mentor
The recent outbreak of Zika virus has been a worldwide cause for concern. The virus causes neurological impairments and is especially detrimental in prenatal development, often leading to microcephaly. Viral proteases are good drug targets because sufficient inhibition of the protease can halt polyprotein processing. Using computational molecular dynamics, potential competitive inhibitors for the NS2B-NS3 Zika virus protease are studied. Clean drug-like molecules from the ZINC online molecular database were computationally docked into the protease using PyRx to give approximate binding affinities. Further chemical modifications were made to the most promising ligands to improve specificity within the active site. Modifications were made to enhance noncovalent interactions such as pi-stacking and hydrogen bonding. Conformational changes in the protease as well as ligand-protease interactions are observed through simulations. The inhibitors displaying the highest binding affinities will be discussed further.
Keywords: molecular dynamics, Zika, inhibition, computational chemistry, protease, biochemistry, free energy, drug discovery
Topic(s):Chemistry
Biology
Presentation Type: Oral Paper
Session: 103-5
Location: MG 1096
Time: 9:00