some of the protein mutants I'm investigating show no binding by means of experimental techniques.
I expected that the free energy variations of these mutants compared to the wild type protein would be very positive. Instead, I found out that these "non-binding" mutants tend to have null variations of free energy compared to the wild type.
I then tried to perform separate MD simulations for each mutant, and the results are very similar, thus these results do not seem to be related to the computational alanine scanning approach. Thus, I'd say they could be outliers.
Is it possible that the predictability of MM/PBSA for the interaction of two non binding molecular species is low, possibly due to the somewhat irrealistic nature of the simulated complex?
Thank you very much in advance!
Dimitrios Spiliotopoulos_________________________________________________________________________________________________ Dulbecco Telethon Institute c/o DIBIT Scientific Institute
Biomolecular NMR Laboratory, 1B4
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