(WHPC01) CHARMM Force Field Parameters for the Zn+ Center of 6‐Pyruvoyl Tetrahydropterin Synthase Enzyme
Women in HPC Poster
Big Data Analytics
TimeTuesday, June 18th12:30pm - 5pm CEST
DescriptionDrug discovery, development and finally commercialization is an expensive and time-consuming process. Computer-aided drug development resolved this matter by allowing speedy identification of potential drug candidates with high binding affinity and selectivity towards selected metabolic targets. Therefore, decreasing the initial number of drug candidates to be lab tested and vastly reducing the time and cost of discovering effective drugs. In this study, computational approaches were used to aid in the discovery of new potential anti-malarial treatments and alternative metabolic targets. Appropriate Force Field (FF) parameters of the active site metal centres from the malaria parasite folate pathway enzyme 6-pyruvoyl tetrahydropterin synthase (PTPS), were derived quantum mechanically and then validated. We employed quantum mechanics (QM) and Potential Energy Surface scans (PESs) to generate the FF parameters and subsequently validated it using all atomics Molecular Dynamics (MD). The newly generated force field parameters will provide accurate and reliable MD simulations of the protein active site, which can improve the computer-aided attempts of identifying potential drug candidates for malaria treatment. The resources available at the Center for High-Performance Computing (Cape Town, South Africa) were utilized to perform the PESs using the Gaussian software package and all atomic MD simulations, using the Chemistry at HARvard Molecular Mechanics (CHARMM) MD-simulations packages, to investigate the validity of the integrated FF parameters. The use of HPC has accelerated and opened new perspectives to this process, allowing the use of parallel processor networks to study our large bio-molecule system. A problem which could not previously be dealt with.