Hydrogen bond networks

A hydrogen bond is a non-covalent interaction between a hydrogen convalently bond to a very electronegative atom (N, O, F) and another very electronegative atom. The interaction in a hydrogen bond is dominantly electrostatic, which leads to a pronounced flexibility in the bond length and angle. However, the distance between X and H, when X = N or O, is most optimal around 2 Å and the angle between the covalent bond and the hydrogen bond between 150º and 180º.
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Hydrogen bond between an electronegative atom (Y)
and a hydrogen (H) linked to an electronegative atom (X).
The angle ϑ is usually around 150-180º.
Hydrogen bond networks are webs or hydrogen bonds that connect the sidechain of multiple residues across the protein.
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A hydrogen bond network as represented with ProteinTools.

Hydrogen bond networks help to stabilize the entire protein structure and have also been observed to play a role in activation and allostery. For example, it has been observed that GPCRs present an extensive hydrogen bond network that spans all functional motifs of the protein in the active state, suggesting it might contribute to their activation mechanism [1].

Ligand binding has also shown to perturb the interresidue interactions and shift hydrogen bond networks, which drive a major redistribution of energy [2].

Given that hydrogen networks can mediate coupling between remote regions of the protein, they are paramount in modulating allostery, function, and stability. Thus, methods to easily compute hydrogen networks in proteins are key to understand protein function.

In ProteinTools, we protonate the user-given protein coordinates with PROPKA [3] and PDB2PQR [4]. Then, we compute all hydrogen networks in the protein sidechains using the Baker-Hubbard algorithm [5]. This algorithm presents cutoffs of ϑ > 120º and d < 2.5 Å.

We thus consider to be in the same network cluster any two residues that have a path of hydrogen bond networks between them.

References