Binding Energy Analysis

[SalahBioPhysics]

This is one @example of how we'll get the ΔΔG

Soon I'll write a conclusion for how a small change in binding energy results in a some (??-fold) change in the equilibrium binding constant.

[jchodera]

Awesome!

Some questions:

• Is the protonation state EUI01A1382 the dominant state in solution?
• Are you fixing the protein protonation states as well, or just the ligand here?

[SalahBioPhysics]

Is the protonation state EUI01A1382 the dominant state in solution? No, in solution the dominant state is EUI+1A1382, and in protein the dominant state is EUI01A1382. (The yellow box in the sheet)

Are you fixing the protein protonation states as well, or just the ligand here? Just the ligand

[jchodera]

Awesome!

Can we see what happens when the protein protonation state is fixed or variable too?

[SalahBioPhysics]

Yes I believe we can. But it may take some time to know what residues to fix. The example above is done by a quick mcce run.

[SalahBioPhysics]

BindingCurves.xlsx

This is quick mcce calculations for inhibitors that change charge upon binding.

Note: 01 means the net charge of the inhibitor is 0 02 means the net charge of the inhibitor is 0, second 0 state +1 means the net charge of the inhibitor is +1 +2 means the net charge of the inhibitor is +1, second +1 state +3 means the net charge of the inhibitor is +1, third +1 state +a means the net charge of the inhibitor is +2 ***+b means the net charge of the inhibitor is +2, second +2 state