key: cord-0939820-5m6s5kqr
authors: Rebehmed, Joseph; de Brevern, Alexandre G.; Sowdhamini, Ramanathan; Joseph, Agnel Praveen
title: Editorial: Advances in Molecular Docking and Structure-Based Modelling
date: 2022-01-27
journal: Front Mol Biosci
DOI: 10.3389/fmolb.2022.839826
sha: efa8bb1cdf9941718020531b2f7f3dd0b2576410
doc_id: 939820
cord_uid: 5m6s5kqr

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The three-dimensional (3D) structures of proteins form the structural framework of their functions. Having access to the structure allows scientists to better apprehend molecular details of protein functions; it is also crucial for protein engineering, e.g., to modify and optimize an enzyme for a certain biochemical reaction; or for designing new and improved drug molecules based on the structure of the target protein. Structures are also needed to investigate how proteins interact; a vast majority of the protein-protein interface residues are involved in extensive intra-protein interactions apart from inter-protein interactions (Jayashree et al., 2019) .

With the increase in protein structures available in the Protein DataBank (PDB, 184,929 entries, on the 11th of December 2021, https://www.rcsb.org) (Berman et al., 2000) , and the recent development of machine learning approaches for protein structure prediction, e.g. AlphaFold2 (Jumper et al., 2021) , it is evident that protein structures will be an essential component of a large number of biological research studies. It also highlights the importance of efficient computational tools to process the structures and derive various biological interpretations.

These in silico methodologies are often complex, have limitations, and the results must be associated with appropriate statistical and quality measures. The objective of this Research Topic was to bring together various contributions based on cutting-edge computational methodologies; these include computational analysis of structures and complexes with developments and applications that integrate docking and molecular dynamics approaches, and complex experimental data such as cryogenic electron microscopy (cryo-EM).

Two articles underline the importance of new computational approaches for evaluating atomic models derived from experimental data or built ab-initio. The first work by Olek and Joseph dealt with the quality of models obtained by cryo-EM. In fact, the final atomic model is often incomplete or contains regions where atomic positions are less reliable or incorrectly built. They presented a software tool for the validation of the backbone trace of atomic models built in the cryo-EM maps. They use the false discovery rate analysis to segregate molecular signals from the background and show how this approach can properly complement current measures Olek and Joseph. Launay et al. tackled the challenging question of scoring in protein-protein docking. They explored several ways to perform consensus-based rescoring. They showed that rescoring performs worse than the traditional physics-based evaluation but the two complement each other and can be used in combination (Launay et al.) .

Classical approaches such as molecular dynamics (MD) are useful to apprehend new biological systems. In this field, Pitard et al. studied the interaction of calmodumin (CaM) with the bacterial virulence factor, Edema Factor (EF). The system is of great interest as orthosteric and allosteric ligands have been proposed to inhibit EF activity. Using state-of-the art MD simulations, they underlined the presence of cavities at the interface between EF and CaM that could be linked to allosteric events Pitard et al.; Tang This special issue is dedicated to the loving memory of Prof. Narayanaswamy Srinivasan who left us too soon on the third of September 2021 (Eisenhaber et al., 2021) . As a passionate scientist and a wonderful human being, he is a true inspiration. May his soul rest in peace.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

The Protein Data Bank

Memoriam of Narayanaswamy Srinivasan

Interface Residues of Transient Protein-Protein Complexes Have Extensive Intra-protein Interactions Apart from Inter-protein Interactions

Highly Accurate Protein Structure Prediction with Alphafold

Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.Copyright © 2022 Rebehmed, de Brevern, Sowdhamini and Joseph. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Frontiers in Molecular Biosciences | www.frontiersin.org