On Wed, Mar 06, 2024, Yang Wei via AMBER wrote:
>
>I am utilizing the MM-PBSA method to compute the binding free energy
>between a protein (residues 1-123) and its (degrader+VHL) (residues
>124-286). The total simulation duration is 400 ns. Following an analysis of
>the RMSD of backbone atoms relative to the X-ray structure, only the last
>200 ns of the simulation were selected for MM-PBSA analysis. However, I
>have encountered a significant standard deviation within my system.
Wow: lots of people want to weigh in here.
I don't see any significant standard deviations in your output. The
standard error in the means are all quite low. The "bottom line" number,
the standard error in the estimate of the binding free energy, is 0.2
kcal/mol for GB and 0.3 kcal/mol for PB (if I am reading your outputs
correctly). These show statistical errors that are pretty much negligible.
Perhaps you mean something else here. The fact that GB and PB estimates of
binding affinities differ by 100 kcal/mol suggests that there is indeed
something seriously wrong somewhere. But the statistical uncertainties in
the two estimates are quite small.
The expected systematic errors, from force field limiations, from errors
inherent in the MMPBSA method itself, and from problems with the GB or PB
calculations, and certainly far larger than these values.
Also, I don't seem to see any entropy estimates in your output files.
So, the resulting numbers cannot be correctly compared to experimental
estimates of free energy changes.
...hope this helps...dac
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed Mar 06 2024 - 20:00:02 PST
