AMBER Archive (2008)

Subject: AMBER: PMF calculation for binding constant or rate constant?

From: Catein Catherine (askamber23_at_hotmail.com)
Date: Tue Apr 15 2008 - 21:26:46 CDT

Dear Sir/Madam,
 
I noted from the literature that sometime the result of potential of mean force was used to calculate the rate constant or binding constant of reaction .
 
I done a Potential of Mean Force calculation for the dissociation of drug from a receptor accords to the binding distance between the active site and the drug. There is not covalent bond between them. I got a contact minima at ~5 A at zero kcal/mol of PMF energy. The free energy profile increase till 10 A at 8 kcal/mol. The free energy level off at 8 kcal/mol after 10 A, which indicate the total removal of drug.
 
I have difficulty to decide if the I shoud use the 8 kcal/mol to calculate the rate constant or the binding constant, as I cannot see an obvious transition state. It is a must that I should be able to observe a clear transition state by PMF calculation? Could it be affected by the methods that I used or the restrainst used in the umbrella sampling?
 
I also noticed that some publication rescale the WHAM result to make the level off (in this case is 8 kcal/mol) to zero, while the minimum was set as a negative values (in this case is -8 kcal/mol). Is it necessary to be done? Why?
 
Please kindly help and many thanks in advanced,
 
Cat
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