Speaker
Description
Probing the Structural Dynamics of the Malaria Parasite Plasmodium falciparum GTP-cyclohydrolase I to Reveal Potential Allosteric Drug Targeting Sites
Computer-aided drug discovery based on high-performance computing (HPC) has become an essential approach in drug discovery research. HPC remarkably improved the efficiency of discovering new drugs and metabolic targets by reducing the time and costs involved in new drugs discovery and development. Consequently, bringing a new era in drug discovery research and facilitate the identification of promising drugs. In this study, the structural dynamics and cooperative motions of the malaria parasite Plasmodium falciparum (P. falciparum) GTP-cyclohydrolase I (GCH1) enzyme were studied to disclose potential allosteric drug targeting sites. Notably, allosteric drugs hold the potential for delivering more selective and less toxic medicines than those targeting active sites. The research study employed the normal mode analysis (NMA) approach based on the elastic network model (ENM) to elucidate the intrinsic dynamics modulating the GCH1 activity and further disclose key sites exerting allosteric effects across its structure. The resources available at the centre for high-performance computing (CHPC) (Cape Town, South Africa) were utilised to construct the ENM models and calculate the normal modes. The use of HPC in this study was crucial as it handled the intensive computations associated with studying such a large protein structure. The NMA of the GCH1 disclosed essential structural information about the protein intrinsic dynamics and the mechanism of its allosteric modulation, which can, in turn, provide a solid starting point to design novel antimalarial drugs against the malaria parasite P. falciparum GCH1 enzyme.
