December 6th CTE Seminar

Title: Utilization of computational techniques to understand protein structure-function relationships and guide drug design

Presenter: Dr. Anne Brown, Assistant Professor, Science Informatics

Research group: Bevan and Brown Lab

Using computational tools to study protein structure-function relationships can enhance knowledge at the atomistic level surrounding biological phenomena and basic mechanisms, while also accelerating drug discovery for protein targets. Current research focuses on the application of computational molecular modeling of macromolecules in order to relate the structure and dynamics of the system to function. Two techniques that we utilize the most are molecular dynamics (MD) simulation and molecular docking. MD simulations provide insight into dynamic properties of molecular phenomena including protein structure-function relationships, protein folding/ misfolding, protein-membrane interactions, and ligand-receptor interaction. Molecular docking and virtual screening offer a time- and cost-effective method to identify potential agonists and antagonists for receptors and inhibitors for enzymes. This work highlights the utilization of these techniques in computer-aided drug design (CADD) to inform knowledge on protein dynamics involved in HIV viral entry (gp41), develop orthologue and isoform-specific inhibitors for sphingosine kinases (SphKs), and highlight potential target structures of protein oligomers involved in amyloid diseases. Ultimately, these computational findings and insights are coupled with experimental collaborators, increasing the impact of the work, understanding of disease states, and guide therapeutic design. The work presented highlights the application of computational techniques in isolation and in conjunction with experimental approaches with multiple collaborators at Virginia Tech. Ultimately, we have provided an increased understanding of protein structure-function relationships and demonstrated promise in drug discovery through the usage of these computational techniques and collaborations.