Which interactions should we report? My compound shows hydrogen bonding alongwith hydrophobic intercations, pi-pi stacking, pi-sulfur stacking, pi-alkyl stacking. Its binding energy is 9.3 which is far greater than standard drug.
Hi,
I am not really a specialist in this specific field, but I study polyelectrolytes, surfactants, dyes and their interactions. Here the most important interactions are non-covalent, electrostatic, hydrophobic and pi-pi-stacking. Being a biochemist I would say non-covalent bonds have far greater flexibility allowing 'induced fit' 'lock and key' models to be applied. The interactions you mention for your compound are by the way all non-covalent. Perhaps the included article can shed some light on which of the interactions you mention is the prevailing one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151162/
Kind regards, Leo
The most significant interactions are those that contribute most to the protein-ligand binding free energy.
First, I guess there's some confusion here, since all listed interaction are non-covalent. Covalent bonds are rarely seen in ligand-protein interactions (with some exceptions) and can't be modelled by standard docking methods.
There is no general answer to the question which interactions are most important, since it depends on the structure fof the ligand and the binding site. There is a lot of ligands which are stabilized mostly by hydrogen bonds, but there are also cases with very nonpolar ligands stabilized in the binding site by hydrophobic / van der Walls interactions. An analysis of the structure of the ligand and the binding pose obtained from docking usually helps in establishing which ones are important - and most docking programs can also partition the (Gibbs free) binding energy of the ligand into specific interactions coming from specific residues to get a better view.
Dear Martin Klvana,
I am using autodock vina. How can I find out which interactions contribute most to the protein-ligand binding free energy.
Dear Dr Talha Bin Emran,
Both them are important...I have the justificative.
Contact me: [email protected]
All the best
Irfan: There is an option in AutoDock Vina to print individual contributions to the intermolecular score; see the output of
"vina --help_advanced" command.
https://www.ncbi.nlm.nih.gov/pubmed/19499576
Focus on the hydrogen bonding (HB) and van der Waals (VDW) interactions. For the HBs, select those that have lengths that are closest to the ideal HB length of 2.80 Angs. For the VDWs, select those that have lengths that are closest to the ideal VDW length specific to the pair of atomic elements that interact -- these values can be found in the literature; I can't recall them offhand, but I do know they do exist. Roughly, they depend on the atomic radii of the two interacting atomic elements.
BTW there are no covalent"interactions" (i.e., bonds) between two docked molecules (by definition). For example, when a ligand is docked into a receptor protein, all interactions between them are non-covalent, e.g., hydrogen bonds and van der Waals interactions. This makes the interaction transient (non-permanent or reversible), and there would be an equilibrium constant for the formation of the protein-ligand complex. If a covalent bond forms between two molecules, that would be a chemical reaction, not a complex formation. Whenever we say "interaction," what we mean is non-covalent (and reversible).
Most of the articles with in silico docking mentioned only about hydrogen bonds interaction
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