Dear Sir/Madam,
I am interested to study the drug dissociation pathways from a receptor. As the drug is surrounded by many proteins residues. By physically looking at the co-crystal structure of drug-receptor complex. The drug can remove the receptor through the gap between residues A and B. or it may also move from the gap between residues C and D. Of courses, there are many more unexpected pathways could become feasible after conformational changes of the protein. I am writing to ask what is the best way to study this questions with AMBER.
I tried to use Potential of mean force with umbrella sampling. I defined the distance between an atom of the receptor and another atom of the drug as the reaction coordinate. I found the drug move into the gap between residue A and B. As the choice of atoms used in the reaction coordinate did not specify the drug to move to the gap between residue A and B. Can I confidently say that the gap between residue A and B is most likely pathway?
If the answer is no. What can I do next? I notice that the RAMD can runs in amber 8. However, I only have amber10, so, I cannot use it.
I know SMD can be used to study the potential of mean force for a drug dissociation. However, I also have to define the atoms used for the reaction coordinates. Can I confidently say that the gap between A and B is most likely dissociation pathway, when I found out of 50 simulation, 40 of them go thr the same or similar pathway, while 5 of them go thr the gap between C and D? Even if in all of the 50 simulations, I has to the define the same atoms in the reaction coordinates.
Best regards,
Catherine
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Received on Sun Aug 29 2010 - 23:30:03 PDT
