Simple Enzyme Reaction

In this tutorial, we will modeling the reaction path  catalyzed by Triosephosphate Isomerase (TIM) enzyme. The reaction consists in the interconversion of the three-carbon sugar dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP), showed in Figure 1. The initial coordinates has been obtained in protein data bank ( http://www.pdb.org/, code = 7TIM). The PDB file consist in two poly peptide chains associated with the reactive intermediate analogue phosphoglycolohydroxamate (PGH).

The chain A was isolated and PGH was modified to DHAP. The system has been built using amber ff99SB (protein portion), tip3p (water model) and GAFF (DHAP molecule). For this tutorial, we will compute the potential energies across the reaction path using a multiple-distance restraint method. For future tutorials, a more robust methodology  will be used to compute the free energy along the reaction path.

https://www.youtube.com/watch?v=JFAS0Muknf8&t=3s

The coordinates and topologies files used in this tutorial can be downloaded here.