| Popis: |
In recent years, coarse grained (CG) models, with a resolution at the residue level for proteins,1,2 have gained great popularity, due to its balance between accessible time scale and detail level. However, because of the coarse description of the residues, electrostatic interactions arising from the electron distribution within the coarse grained beads are lost, and the model fails to consistently reproduce protein secondary and tertiary structure. Therefore additional restraints stabilizing the initial structure are imposed, allowing the CG model to maintain the correct structural scaffold,3 but impairing the ability to study protein conformational changes.Here I will present a study comparing the capability of selected CG models to describe the conformational change of a two-domain protein that undergoes fully closure upon ligand binding. With the proposed domELNEDIN model, where an elastic network is set up only internally in the protein domains, we are able to observe the expected conformational change. To also improve the description of the protein-ligand interaction in the CG model, representations of the ligand using bead types similar to those introduced recently for polarizable CG water4 were tested.(1) Marrink, S. J. et al, J. Phys. Chem. B 2007, 111, 7812-7824.(2) Monticelli, L. et al, J. Chem. Theory Comput. 2008, 4, 819-834.(3) Periole, X. et al, J. Chem. Theory Comput. 2009, 5, 2531-2543.(4) Yesylevskyy, S.O. et al, PLoS Comput. Biol. 2010, 6. |
