Special Issue "Evolution and Structure of Proteins and Proteomes"
Deadline for manuscript submissions: 31 May 2018
The evolution of proteins and proteomes is governed by a wealth of interacting processes, spanning from the population level to the atomic level. When a mutation appears in a protein coding sequence, its ultimate fate in a population depends, in part, on its effects on functional sites, folding and stability, and expression. Even subtle modifications to any of these components can have downstream effects on systems-level processes that influence individual fitness. Although these molecular processes occur within an individual, their evolutionary consequences are determined by the population into which they are cast. In this Special Issue, we encourage the contribution of review articles and original research papers that examine the evolution and structure of proteins and proteomes through a merger of biophysics, systems biology, evolutionary, and population genetic frameworks.
Dr. David Liberles
Dr. Ashley Teufel
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 papers will be 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. Genes 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 1600 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.
- molecular function
- biophysical models
- evolutionary systems biology
- biological networks
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Tentative title: Evolutionary divergent suppressor mutations in conformational diseases.
Authors: Noel Mesa-Torres1, Isabel Betancor-Fernández2, Eduardo Salido2 and Angel L. Pey1*.
1 Department of Physical Chemistry, University of Granada, Granada (Spain).
2 Hospital Universitario de Canarias, Tenerife (Spain).
* correspondence: email@example.com
Tentative abstract: Neutral and compensatory mutations are key players in the evolutionary dynamics of proteins at molecular and organismal levels. Conversely, largely destabilizing mutations are rarely tolerated by evolution, although their occurrence in diverse human populations has important roles in the pathogenesis of conformational diseases. We have recently proposed that divergence at certain sites from the consensus (amino acid) state during mammalian evolution may have rendered some human proteins more vulnerable towards disease associated mutations, primarily by decreasing their conformational stability. We extend and refine here this hypothesis discussing results from phylogenetic and structural analyses, structure-based energy calculations and structure-function studies at molecular and cellular levels. As proof-of-principle, we will focus on different mammalian orthologues of the NQO1 (NAD(P)H:quinone oxidoreductase 1) and AGT (alanine:glyoxylate aminotransferase) proteins. The results will be discussed in terms of the different loss-of-function pathogenic mechanisms associated to these enzymes, including enzyme inactivation, accelerated degradation, intracellular mistargeting and aggregation. Last, the potentially higher robustness of mammalian orthologues containing certain consensus amino acids as suppressors of human disease, and their relation with different intracellular post-translational modifications and protein quality control capacities, will be discussed as sources of phenotypic variability between human and mammalian models of disease.
Tentative title: Epistatic interactions in NS5A of Hepatitis C virus explain drug resistance mechanisms
Authors: Elena Knops 1, Saleta Sierra 1, Prabhav Kalaghatgi 2 Eva Heger 1, Rolf Kaiser 1, and Olga V. Kalinina 2,**.
1 German Center for Infection Research (DZIF) – Cologne-Bonn Partner Site; Institute of Virology, University of Cologne, 50935 Cologne, Germany; firstname.lastname@example.org
2 German Center for Infection Research (DZIF) – Saarbrücken Partner Site; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany; email@example.com
* Correspondence: firstname.lastname@example.org; Tel.: +49-681-9325-3004
Tentative abstract: Hepatitis C virus (HCV) causes a major health burden and can be effectively treated by direct-acting antivirals (DAAs). NS5A, which plays a role in the viral genome replication, is one of the DAAs targets. Resistance-associated viruses (RAVs) harboring NS5A resistance-associated mutations (RAMs) have been described at baseline and after therapy failure. Q30R is a characteristic RAM for the HCV sub/genotype (GT) 1a but corresponds to the wild type in the GT-1b; still, GT-1b strains are susceptible to NS5A-inhibitors. In this study, we show that GT-1b strains with R30Q often display other specific NS5A substitutions, particularly in positions 24 and 34. We demonstrate that secondary substitutions usually happen after initial R30Q development in the phylogeny of the 1b sequences, and that the chemical properties of the corresponding amino acids serve to restore the positive charge in this region, acting as compensatory mutations. These findings may have implications for RAVs treatment.