Official Project Description
In this project we simulate the protein Phosphoglycerate kinase (PGK), a vital component in cell metabolism (specifically glycolysis, the processing of sugar into ATP for the cell).
PGK catalyzes the conversion of 1,3 bisphosphoglycerate to 3-phosphoglycerate generating one molecule of ATP in the process.
While the biochemical activity of PGK has been long understood, how this process is achieved from a structural perspective is less well known. PGK deficiencies lead to hemolytic anemia and myopathy, over-expression has been linked to a variety of cancers, and PGK can metabolize a variety of different drugs.
We hope that simulations of PGK will lead to a better understanding of how PGK completes these essential catalytic activities. In our prior projects we have looked at the impact of ligands on PGK conformations.
As our experimental collaborators have several biophysical measurements of PGK, we also believe this gives us an excellent opportunity to assess how force fields, one of the fundamental processes of our computer simulations, affect the accuracy of our simulations.
In project 18224, we looked at a commonly used force field, charmm36 performed.
In 18227-18230 we look at how the force fields amber03 (18227), amber14sb (18228), and amber19sb (18230) perform with their cognate water models.
We believe these findings will aid not only this project, but all simulation projects going forward.