xiki-tempula
commented
9 months ago @mrshirts Thanks for the review. I think one paragraph is a bit not very clear. Do you mind have a look at my suggestion and change this part, please? Thank you. I'm happy with the other part of the changes. Do you mind merge this PR when you are happy? Then I will
- add a figure and paragraph to show the solvation free energy and shorten the part with regard to the ABFE.
- Also reduce the number of times alchemical analysis is being mentioned.
mrshirts
Thanks for getting this going, @xiki-tempula!
I did a first pass through for text revision.
Overall comments - I think we could potentially cut out some of the discussion about absolute binding free energy theory, including the thermodynamic cycle figure, because it requires two calculations, and alchemlyb doesn't actually compute cycle closure. It might be better to just talk about a solvation free energy, which can be done in one calculation, show a figure on how that works, and then mention in 1-2 sentences how alchemlyb calculations can be plugged into different thermodynamic cycle to obtain relative and absolute binding free energies.
i.e. section that could be simplified because it doesn't really talk about what alchemlyb does its. "The binding free energy of a drug within a protein is defined as the disparity in free energy between the drug's end-state in the protein's binding pocket and its alternative end-state in a solution, typically water. Absolute binding free energy calculations employ a thermodynamic cycle that establishes a connection between these two end-states through two alchemical legs, namely the bound and free legs (Figure 1). In the bound leg, the drug is decoupled from the binding pocket, while in the free leg, the same drug is decoupled from the solvent. The resulting free energy difference represents the energy required to transfer the drug from the solvent to the protein binding pocket, constituting the binding free energy of the drug."
I also thing that it repeats a bit much that it's a successor to alchemical analysis; that's stated multiple times.
Great draft!