I was able to successfully locate and confirm TS for my glycoside hydrolysis reaction. As the next step i thought performing molecular docking followed by SMD QM/MM calculation.
In doing so i understand performing molecular docking means using lower level of theory.
Furthermore my TS also contains an active site residue intact. Hence i cant use the TS as it is due to the presence of the same resiue in original crystal structure and i dont suppose it is a good approach to remove residue part from TS because then it would change the TS entirely.
I really appreciate any suggestion or otherwise on this matter.
Thank you
Docking is very unlikely to produce a good initial guess for TS geometry. It might be better to manually insert the substrate in to the active site. Try to minimize the atom clashes during this process. There are some articles you may look into: Article Mechanism of proteolysis in matrix metalloproteinase-2 revea...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818682/
And here is a good tutorial which may be helpful: http://chem.wayne.edu/schlegel/Software/oniomtoolTAO/TAOtutorial.html
If you pretend to do QM/MM and you have the structure of the complex, you don't need docking. But if you don't have the complex, the docking will generate starting complexes for QM/MM. You can start from different complexes and see how your system evolve.
Dear Mr. Uttam Pal and Mr. Ihosvany Camps,
I already have the TS identified separatly. I need to combine it with the rest of the enzyme so as to make a complex beforehand MD. Hence i thought of performing docking with certain constraints if possible.
But as i mentioned earlier my TS has certain residue parts intact which are originally available with the enzyme. So how would one solve this kind of a problem?
If you know the geometry and charge distribution of the transition state, you can define valence bond states and simulate the reaction using Empirical Valence Bond (EVB) approach.
Article Empirical valence bond calculations of enzyme catalysis
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