1
$\begingroup$

Why are (non-polar) hydrogen atoms generally neglected in a protein-ligand (or drug) binding energy calculation? They do have charge and mass. Doesn't that affect the free energy calculation?

The relevant equations are given here: $$ \Delta G_\text{bind} = -RT\ln K_\text{d} $$ $$ K_\text{d} = \mathrm{\frac{[Receptor][Acceptor]}{[Complex]}} $$ $$ \Delta G_\text{bind} = \Delta G_\text{desolvation} + \Delta G_\text{motion} + \Delta G_\text{configuration} + \Delta G_\text{interaction} $$


A system where this is the case would be the following, note that only the polar hydrogen atoms are explicitly represented.

System with polar hydrogen atoms marked out.

$\endgroup$
  • 2
    $\begingroup$ are you referring to computer simulations of protein-ligand interactions? $\endgroup$ – user137 Aug 18 '14 at 15:19
  • 1
    $\begingroup$ @user137: Yes, I want to know while calculating the above mentioned binding energy(free energy difference), why we neglect non-polar hydrogen. $\endgroup$ – Devashish Das Aug 18 '14 at 16:00
  • $\begingroup$ @DevashishDas because their influence is very, very small? But yes, generally it should be considered, especially if zero energy correction is used. $\endgroup$ – permeakra Aug 19 '14 at 0:12
  • 1
    $\begingroup$ What kind of calculation are you referring to? Quantum chemical or molecular mechanics, molecular dynamics, empirical values, semiempirical, monte carlo simulations, or a mixture of the previous? Are solvent effects considered? How rigid and how large is the system? Could you elaborate a little more about these parameters, please. $\endgroup$ – Martin - マーチン Aug 19 '14 at 1:04

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Browse other questions tagged or ask your own question.