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

Alexandre Victor Fassio,Letícia Xavier Silva Cantão,Vitor Pimentel,Luana Luiza Bastos,Diego Mariano,Leonardo Henrique Franca De Lima,Pedro Fischer,Raquel Cardoso De Melo-Minardi

doi:10.3389/fbinf.2021.730350

Alexandre Victor Fassio, Letícia Xavier Silva Cantão + Show 6 more

Open Access

https://doi.org/10.3389/fbinf.2021.730350

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Abstract

Evolutionarily related proteins can present similar structures but very dissimilar sequences. Hence, understanding the role of the inter-residues contacts for the protein structure has been the target of many studies. Contacts comprise non-covalent interactions, which are essential to stabilize macromolecular structures such as proteins. Here we show VTR, a new method for the detection of analogous contacts in protein pairs. The VTR web tool performs structural alignment between proteins and detects interactions that occur in similar regions. To evaluate our tool, we proposed three case studies: we 1) compared vertebrate myoglobin and truncated invertebrate hemoglobin; 2) analyzed interactions between the spike protein RBD of SARS-CoV-2 and the cell receptor ACE2; and 3) compared a glucose-tolerant and a non-tolerant β-glucosidase enzyme used for biofuel production. The case studies demonstrate the potential of VTR for the understanding of functional similarities between distantly sequence-related proteins, as well as the exploration of important drug targets and rational design of enzymes for industrial applications. We envision VTR as a promising tool for understanding differences and similarities between homologous proteins with similar 3D structures but different sequences. VTR is available at http://bioinfo.dcc.ufmg.br/vtr.

Highlights

Proteins are macromolecules responsible for most functions in living beings, such as transport, immune protection, control growth, and so on (de Melo et al, 2006)
We suggest that PDBs present similar folding, but if structures with different folds were used, VTR would try to perform the best structural alignment using the TM-align tool
VTR allows three search methods: 1) ALL, which calculates all interactions for both whole complexes; 2) SINGLE, which calculates contacts in a single chain for each protein and compares them; and 3) PPI, which calculates protein–protein interactions in both complexes and compares them

Summary

Introduction

Proteins are macromolecules responsible for most functions in living beings, such as transport, immune protection, control growth, and so on (de Melo et al, 2006). The understanding of how the polypeptide sequences fold into a particular three-dimensional shape after synthesis remains a VTR: A Web Tool for Comparing Contacts mystery (Science, 2005; Upadhyay, 2019). It has motivated the search for computational algorithms to predict protein structures from their sequences (Dill et al, 2008; Dill and MacCallum, 2012) or even detect and annotate protein functions correctly (Veloso et al, 2007; Franciscani et al, 2014; Silveira et al, 2014). Understanding protein structures and their interactions accurately is crucial to molecule’s rational design for several applications, including discovering novel drugs and improving enzymes for the biotechnological industry (Kuntz, 1992; Barroso et al, 2020)

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