Structural bioinformatics strategy in the design of antiviral drugs from natural products

Описание: Speaker: Professor Habibah A. Wahab, Dean, School of Pharmaceutical Sciences, University of Science, Malaysia.

Abstract:
Structural bioinformatics has emerged as a powerful tool to approach the development of structure based drug design (SBDD) due to the availability of vast experimental data generated from X-ray crystallography and NMR spectroscop. These experimental data are important in elucidating atomic details of ligand-target complex. However, in some cases, the structures obtained through these experiments cannot be used directly in SBDD because of significant changes between apo and ligand-bound forms. To overcome this limitation and gain additional insight into the motions occurring during ligand-binding, molecular dynamics simulation is frequently utilised as it allows an improved conformational space sampling.

In this talk, I will underline recent advances in the methodologies as well as their application to influenza and dengue antiviral design. I will also highlight some of our works that applied these methods in our quest to better understand how chemical modifications in a series of ligands synthesised from Malaysian natural product scaffolds bring about changes in their binding affinities (structure-activity relationships). From this understanding, we discovered compounds from cinnamic acid as well as lawsone scaffolds which possessed potential antiviral activities at submicromolar concentrations.