Event date:
May 10 2023 2:30 pm

An Integrated High Throughput XFMS and MD Simulation Approach to Investigate Protein Conformational Landscape and Protein – Water Networks

Dr. Safee Ullah Chaudhary
Maham Hamid
Room 10-301, SBASSE Building (third floor)
PhD Synopsis defense


The biological activity of certain proteins is regulated by ligands which do not directly bind at the active site to make products rather induce conformational alterations. Such allosteric binding of a ligand or any post translational modification results in reshaping of protein conformational landscape. Current techniques provide very little information regarding energy distribution and conformational dynamics of protein allostery. To elucidate these concepts, an integrated X-ray hydroxy-radical footprinting with mass spectroscopy (XFMS) and MD simulation approach that can provide residue level resolution has been proposed. This integrated methodology will provide a powerful computational approach to probe the allosteric effects. To validate this methodology, I have chosen the model protein Escherichia coli (E.coli) CheY - a small protein with a single surface for binding that belongs to a large bacterial superfamily and is part of two-component regulatory system. To cater for the unavailability of open-source algorithms for XFMS data analysis, I have built a high throughput toolbox to analyze the XFMS data. The proposed approach also considers bound water as a part of the complex global landscape. In addition to the XFMS analysis, MD simulation and protein- water hydrogen bond network analysis will be performed to capture the collective motion of proteins constituent atoms and to identify important water nodes. Lastly, the complex information will be reduced to certain diagnostic measures that can differentiate among the various states of CheY protein. This high throughput integrated analysis will furnish a comprehensive understanding of the complex landscape of protein folding and conformational dynamics which can further be implemented in various fields like drug discovery, disease development etc.


PhD Committee Members:

Dr. Safee Ullah Chaudhary (Supervisor)

Dr. Shahid Khan

Dr. Muhammad Tariq

Dr. Muhammad Shoaib