[gmx-users] standard state correction of delta G from a PMF

[chris.neale at utoronto.ca]

Dear Elio:

First, you need to convert your PMF to a free energy difference  
between states. That means defining a boundary between, for example,  
bound and unbound states. The integrate your PMF over the bound and  
unbound states to get two dG values, and their difference is your free  
energy of binding.

Next for the standard state correction that is required to convert  
this free energy of binding into a standard state free energy of  
binding. This is necessary because the volume available to the unbound  
state affects the dG value. In the simplest case, you are going to  
calculate the concentration of your ligand in the unbound state and  
make a volume-based energetic correction to the dG value to align the  
dG with a 1M concentration of unbound ligand.

This may be a little more complex depending on how did your  
simulations (US vs. FEP for example) but still the whole idea behind  
this is that you need to report values for dG at 1M concentration of  
ligand.

There may be other corrections that you require, but if you're having  
trouble with this concept then you should move to a simple system for  
now.

If you still have trouble, then your next post should include thinks  
like "I tried this... but I didn't understand this specific part...."  
to make it clear that you have put in the effort here.

Chris.

-- original message --


Hello. I was wondering if anyone could explain how to convert delta  
G's from a PMF (generated by umbrella sampling and WHAM) into standard  
state values? There are some posts here on how to do this, but are too  
mathematical for me to figure out. I also found the same problem when  
reading some papers that do standard state correction. So if anyone  
has the time to explain this again in a more basic manner it would be  
appreciated. Thanks.

Elio Cino