Hi All,
I'm trying to predict whether heteroatoms (S or O) in my ligand can form non-bonding interactions (See JACS, 2013, 135, 10475) with amino acids such as a Methionine or Cysteine in my protein active site as a possible explanation for selectivity and potency. From the docked poses it does appear that the heteroatom comes reasonably close to the sulfurs in the amino acids (around 3.5 Angstrom). Is there a modeling software that can estimate the strength of the interaction between these heteroatoms in the complex?
Thank you so much for your time and comments!
for non-bonded interactions you can try to build model systems (reduce your system to several atoms) and then try to calculate inter-molecular energies using ab initio software (gaussian, gamess, nwchem, orca)....similar like for instance dispersive interactions.
This topic has been covered before here (see first link below and references within).
It is important to be aware that the results you will get for calculating non-bonded interactions will be highly sensitive to the method you use - so you must choose carefully!
Ideally you would use some high level explicitly correlated method such as CCSD(T)-F12, but this may prove too computationally expensive for systems larger than 10 or so heavy atoms. (See Sherrill, Takatani and Hohenstein linked below)
Some cheaper methods such as Hartree-Fock or standard DFT (with no dispersion correction) are known to model these interactions very badly. There are now DFT methods which model dispersion forces with an empirical corrections term. (See Grimme et al and Jan Jensen's blog post.
https://www.researchgate.net/post/Using_Gaussian_Gaussview_how_can_I_calculate_the_non-bonding_interaction_between_two_molecules
http://molecularmodelingbasics.blogspot.de/2013/03/dft-d-dft-d2-and-dft-d3-density.html
Article An Assessment of Theoretical Methods for Nonbonded Interacti...
Article A Consistent and Accurate Ab Initio Parametrization of Densi...
Thank you for the detailed answer, Patrick. I am a novice when it comes to advanced methods - so have some reading to look forward to!
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