VTR: A Web Tool for Identifying Analogous Contacts on Protein Structures and Their Complexes

Area of Science:

• Structural biology
• Bioinformatics
• Protein interactions

Background:

• Evolutionarily related proteins often share similar structures despite sequence divergence.
• Inter-residue contacts are crucial for stabilizing protein structures and understanding protein function.
• Identifying analogous contacts is key to deciphering functional similarities in proteins with low sequence homology.

Purpose of the Study:

• Introduce VTR, a novel method for detecting analogous contacts in protein pairs.
• Evaluate VTR's utility in comparing proteins with similar structures but dissimilar sequences.
• Demonstrate VTR's potential in drug target exploration and enzyme design.

Main Methods:

• VTR performs structural alignment between protein pairs.
• The method identifies non-covalent interactions occurring in structurally similar regions.
• Case studies involved myoglobin/hemoglobin, SARS-CoV-2 spike protein/ACE2, and β-glucosidase enzymes.

Main Results:

• VTR successfully detected analogous contacts in diverse protein pairs.
• The tool highlighted functional similarities between distantly related proteins.
• Case studies showcased VTR's applicability in analyzing protein-protein interactions and enzyme variants.

Conclusions:

• VTR is a valuable tool for understanding functional similarities in homologous proteins with divergent sequences.
• The method facilitates the exploration of drug targets and the rational design of industrial enzymes.
• VTR provides insights into the relationship between protein structure, contacts, and function.