Designing anti-influenza aptamers: novel quantitative structure activity relationship approach gives insights into aptamer-virus interaction.

This study describes the development of aptamers as a therapy against influenza virus infection. Aptamers are oligonucleotides (like ssDNA or RNA) that are capable of binding to a variety of molecular targets with high affinity and specificity. We have studied the ssDNA aptamer BV02, which was designed to inhibit influenza infection by targeting the hemagglutinin viral protein, a protein that facilitates the first stage of the virus' infection.

Biasing conformational ensembles towards bioactive-like conformers for ligand-based drug design.

Importance Of The Field: In silico or virtual screening has become a common practice in contemporary computer-aided drug discovery efforts and currently constitutes a reasonably mature paradigm. Application of ligand-based approaches to virtual screening requires the ability to identify the bioactive conformers of drug-like compounds as these conformers are expected to elicit the biological activity. However, given the complexity of the energy potential surfaces of such ligands and in particular those exhibiting some degree of flexibility and the limitation of contemporary energy functions, this is not an easy task.

Bioactive conformational biasing: a new method for focusing conformational ensembles on bioactive-like conformers.

Computational approaches that rely on ligand-based information for lead discovery and optimization are often required to spend considerable resources analyzing compounds with large conformational ensembles. In order to reduce such efforts, we have developed a new filtration tool which reduces the total number of ligand conformations while retaining in the final set a reasonable number of conformations that are similar (rmsd < or = 1 A) to those observed in ligand-protein cocrystals (bioactive-like conformations). Our tool consists of the following steps: (1) Prefiltration aimed at removing ligands for which the probability of finding bioactive-like conformations is low.