Advances in Difficult Protein–Protein Interaction Determination

Dear Colleagues,

The field of structural biology has recently seen tremendous advances in the identification and characterization of macromolecules, with breakthroughs in cryo-microscopy at the angstrom level and the high-fidelity, large-scale prediction of protein structures using deep-learning approaches, as demonstrated by AlphaFold2. With the COVID-19 pandemic outbreak, it became very obvious that for some proteins, even if it was possible to routinely detect and express them, it is still very challenging to resolve their atomic arrangement. Many proteins are membranous and require dimerization or even a higher order of organization. Although difficult to resolve experimentally, these proteins are essential to cell function, for mediating transient protein–protein interactions, triggering cell activation after cytokine stimulation, or determining cell fate via apoptosis activation. Many membrane proteins are also key targets for pharmaceutical purposes; for instance, half of the drugs approved by the FDA target a GPCR member. Although important scientific breakthroughs have recently been made, there is still a fundamental need for adding knowledge in protein interactions in membranous or cytosolic compartments. This Issue aims to present advances in protein–protein interactions where symmetry is important for structure and/or function. Authors submitting manuscripts for this Special Issue should cover one or more of the following topics: membrane protein, intrinsically disordered proteins/segments, pore formation, macromolecular assembly, protein–DNA interactions.

Prof. Dr. Alexandre G. de Brevern
Dr. Stéphane Téletchéa
Dr. Jérémy Esque
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Symmetry is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• protein–protein interactions
• membrane proteins
• intrinsically disordered proteins
• macromolecular assembly
• protein–DNA complex

Title: Significance of symmetry in ion channel design
Authors: Marc Baaden
Affiliation: CNRS, France
Abstract: Symmetry is an important design principle of ion channels. Since these channels are responsible for the movement of charged particles across cell membranes, their structure must be carefully designed to ensure optimal function. Here I discuss aspects related to symmetry and function for the pentameric ligand-gated ion channel GLIC with fivefold symmetry. These complex symmetries are thought to provide stability to the channel structure and play a role in certain functions of these ion channels.

Title: Advanced methods for protein-protein prediction and analysis
Authors: Elena Alvarez-Sanchez; Romain Launay; Ragousandirane Radjasandirane; Joseph Rebehmed; Isabelle André; Alexandre G. de Brevern; Jérémy Esque; Stéphane Téletchéa
Affiliation: 1. Department of Computer Science and Mathematics, Lebanese American University, Beirut 1102 2801, Lebanon 2. Université de Paris, INSERM, BIGR, F-75014 Paris, France 3. Toulouse Biotechnology Institute (TBI), CNRS, INRAE, INSA, 31077 Toulouse, France 4. US2B, Nantes University, 44322 Nantes, France
Abstract: Protein-Protein Interactions (PPIs) are known for performing various functions which are essential for all living cells. PPIs build a network, named interactome, which is dynamic and highly complex. Therefore, the molecular interactions between proteins could be more or less specific and are mostly classified into two categories, (i) permanent and (ii) transient interactions. Although experimental approaches have been developed to tackle this issue, many PPIs remain to be discovered or elucidated, especially at structural level. Thus, the use of computational methods seems to be a promising and alternative approach to fill the gap. For many years, a huge effort has been done to develop computational tools for predicting PPIs. To do so, standard initial methods used geometrical and energetical properties, called physics-based approaches. Then, (co)-evolutionary information based on amino acid sequences have been added to improve the prediction. Thanks to Artificial Intelligence (AI), especially machine and deep learning, helped to level up the prediction accuracy. Beyond the prediction, the assessment of the results is a crucial step and several properties could help to discriminate the most probable biological interfaces. Finally, this work aims to review advances and discuss limitations of the state of the art in this field.