Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
Recent advances in computer software and hardware combined with the exponential growth of biological information render in silico methods essential in rationally designing new antiviral and anticancer drugs. This talk will describe two successful drug discovery examples driven by computers and validated experimentally. The first illustrates how computer simulations were used to understand the mode of action of hepatitis C virus (HCV) inhibitors, namely the NS5A polymerase and NS5A scaffold protein. In both cases, computer modelling identified the exact mode of binding of the known inhibitors of these proteins and helped in designing new modulators for their activities. This talk will also discuss how sophisticated modeling techniques combined with the massive high performance computational power of modern IBM supercomputers can be used to identify the atomic interactions of anti-HCV drugs within their targets for different HCV genotypes and for several reported resistant mutations. The second example in this talk describes a new approach in cancer immunotherapy that can activate the immune system to recognize and cure cancer. These new drugs target the immune checkpoints proteins, activate T cells and breakdown their tolerance toward tumours. Our group is actively working on designing and developing these immunotherapy drugs employing sophisticated modelling approaches combined with immunological and biochemical validation technologies. This talk will describe for the first time how these proteins interact at the atomic level and how these models are being used to rationally design small molecule inhibitors for their activities.