[gmx-users] Binding Energy to Binding affinity (Kd)

[Du Jiangfeng (BIOCH)]

Dear Everyone,

I have two questions about the conversion of binding energy to binding affinity. 

I predicted the binding energy of a protein-membrane complex by umbrella sampling (based on Justin's tutorial). After sampling, the binding energy should be the substract of (min-max) PMF. I have repeated the simulation 12 times, and then I have done umbrella samplings also 12 times, then got 12 binding energies which varies from -200 Kcal/mol to -100kcal/mol, does the value vary too much? or is it reasonable since the simulation results can be different? Are those values too huge?  

When I tried to convert the binding energy to Kd by the formula deltaG=-RTlnK, I am frustrated by the kd value. If the binding energy is -100kcal/mol, the kd is calculated as 3.35e-59  μM.  The kd is 1.77e-126  μM when binding energy is -200kcal/mol. This is impossible.  But what is going wrong? 

I appreciate any reply.

Thanks,

    Jiangfeng Du, PhD Student
    Cardiovascular Research Institute Maastricht
    Department of Biochemistry
    P.O. Box 616
    Mobile: +31-681741859
    FAX: +31-43-3884159
    6200 MD Maastricht
    The Netherlands