DOVSA · Development of Virtual Screening Algorithms: Exploring Multiple Ligand Binding Modes Using Spherical Harmonic Consensus Clustering

This project will advance the state of the art in virtual drug screening by developing novel spherical harmonic-based consensus clustering algorithms. The main disease that will be targeted in this project is the acquired immune deficiency syndrome (AIDS), caused by the human immuno-deficiency virus (HIV). However, the approach will be quite generic and will be broadly applicable to many other diseases. The approach will be tested and validated using 40 well-known drug targets from the DUD dataset. It will then be used to screen the French Chimiothèque Nationale library of some 36000 compounds for novel ligands which will bind the CCR5 co-receptor and hence block HIV infection. A small list of candidate entry-blocking compounds will be sent to Barcelona for experimental testing. By extending the SH-based consensus clustering technique, this project will provide a generic tool to help deal with cases where multiple ligands may be associated with multiple pocket sub-sites or which may bind multiple targets, and it will help to find new HIV entry-blocking compounds.