Depending on the exact state of the oxygen, it can either serve as hydrogen bond donor, acceptor or both, and thus participate in a hydrogen bond. Hydrogen bond donors and acceptors on the surface of the unliganded receptors form hydrogen bonds to water, and desolvating these is highly unfavorable, unless they can ve replaced by a hydrogen bond to the ligand.

So, burying a hydrogen bond acceptor or donor on either the ligand or the receptor without replacing it by a hydrogen bond across the interface decreases the docking score, while formation of a hydrogen bond across the interface will increase the score.

Thank you Professor Annemarie Honegger

Please share any reference regarding it.

Well, my answer is a very quick summary of decades of experience in protein design.

For a rough idea of the energies involved: a single O-H : O Hydrogen bond has an energy of up to 5 kcal/mol, compared to the typical folding energy of a typical single domain protein of 5 to 15 kcal/mol

Have a look at the wikipedia article on hydrogen bonds and the articles cited therein:

https://en.wikipedia.org/wiki/Hydrogen_bond#:~:text=The%20energy%20of%20a%20hydrogen,fully%20covalent%20or%20ionic%20bonds.

To give some references:

from https://www.nature.com/articles/s41596-021-00597-z

A practical guide to large-scale docking

Brian J. Bender, Stefan Gahbauer, Andreas Luttens, Jiankun Lyu, Chase M. Webb, Reed M. Stein, Elissa A. Fink, Trent E. Balius, Jens Carlsson, John J. Irwin & Brian K. Shoichet

"Ligand poses are evaluated using a physics-based scoring function (Escore) combining VDW, electrostatic (ES) and ligand desolvation (lig_desol) energy terms (Equation 1):

E(score)=EVDW+EES+Elig-desolv "

Generally, desolvatizing hydrophobic surfaces is favorable as it increases solvent entropy, while desolvatizing hydrogen bond donors and acceptors is unfavorable since it involves the breaking of hydrogen bonds to the solvent

See: https://www.cambridgemedchemconsulting.com/resources/solvation.html

Generally, in ligand binding as in protein folding, desolvation of hydrophobic surfaces provides the driving force of the process, while the burial of hydrogen bond acceptors and donors and the formation of hydrogen bonds provides specificity, as the net energetic contribution is given by the energy gain from the formation of a hydrogen bond minus the energy cost of desolvating the binding partners.

Search Google Scholar for articles linking desolvation energies to docking scores:

https://scholar.google.ch/scholar?q=desolvation+energy+docking+score&hl=en&as_sdt=0&as_vis=1&oi=scholart

Thanks a lot professor