Computational methods such as Molecular Dynamics (MD) simulations are powerful and capable of contributing significantly to our understanding of conformational changes of proteins and other biomolecules. MD simulations have been at the forefront of macromolecular simulations that can provides links between structure and dynamics by enabling exploration of the conformational energy landscapes accessible to protein molecules that are often unobservable in conventional biophysics methods. Additionally, MD simulations have proved to be very valuable in the ability to reveal and characterize conformational changes in proteins and have become a widely used tool in the field of drug discovery. Human Phosphoglucose Isomerase (hPGI) is of particular medical interest as the deficiency of hPGI leads to non-spherocytic haemolytic anemia disease; it is also a biomarker because of its high level of expression in patients with certain cancers. Human PGI has been shown to have a very spatially extended active site. Previous work showed that mutations of residues predicted to be important in the second and third shells resulted in observed substantial reductions of the catalytic rate constant, in some cases by two or three orders of magnitude and in one case eliminating detectable activity altogether. From these biochemical assay results, six variants were chosen, and model structures were built to investigate the structural dynamics that may play a role in observed 100-fold or more decrease in activity. MD simulations of the WT hPGI and six variants are being performed to investigate shifts in dynamics that may affect activity due to mutations at second and third shell positions compared with WT hPGI. <br/>

Role of remote residues in the dynamics and function of human phosphoglucose isomerase

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.