News By Year

2022

2021

2019

April

New publication in The Journal of Molecular Biology. This work describes an update version of the original GUILDify, GUILDify v2.0 a network-based tool to identify disease-causing genes. GUILDify v2.0 represents a major update and improvement of the original method, where we have included protein interaction data for seven species and 22 human tissues and incorporated the disease–gene associations from DisGeNET. To infer potential disease relationships associated with multi-morbidities, we introduced a novel feature for estimating the genetic and functional overlap of two diseases using the top-ranking genes and the associated enrichment of biological functions and pathways (as defined by GO and Reactome). The analysis of this overlap helps to identify the mechanistic role of genes and protein–protein interactions in comorbidities. Finally, we provided an R package, guildifyR, to facilitate programmatic access to GUILDify v2.0 This work is the results of our long-term collaboration with Prof Oliva from the Universitat Pompeu Fabra in beautiful Barcelona. We plan to include GUILDify in future releases of the InteractoMIX platform. The paper is available at or can be downloaded from .

February

New publication in Annals of Botany. This publication presents the results of combining a BAC-based physical map for Lolium perenne (perennial ryegrass), a widely cultivated forage and amenity grass, with GWAS sutides to identify a number of candidates genes associated with heading date, plant width, plant biomass and water-soluble carbohydrate accumulation. Besides the identification of candidates genes, the physical maps will aid validating future sequence-based assembly of the L. perenne genome. The paper is available at or can be downloaded from .

2018

November

New publication in Molecular Cell. The post-translational modification of key residues at the C-terminal domain of RNA polymerase II (RNAP2-CTD) coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases, including cancer. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells. This work has been done in collaboration with Prof Beato from the Center for Genomic Regulation and Prof Oliva from the Universitat Pompeu Fabra in beautiful Barcelona. The paper is available at or can be downloaded from .

August

New publication in Nature Communications. This work describes a the identification of small drug-like compounds to target RAS-mediated interactions. RAS family of proteins is among the most frequently mutated in human cancers. Among these mutations are those impeding the inactivation of RAS and thus resulting in constitutively active mutants. In this work, a RAS antibody fragment was use to screen a library of chemical compounds and detect those competing for binding to RAS. The initial hits were optimized by structure-based design resulting in a series of potent RAS-binding inhibitors able to prevent RAS interactions inside cells. We contributed our expertise to this project on Prof Terence H Rabbitts' group at MRC Weatherall Institute of Molecular Medicine as part of our long term collaboration. The paper is available at or can be downloaded from .

June

Belated congratulations to Eleni who successfully defended her PhD on June 18th, thus, Dr Ioannou from now on. Eleni set to develop novel, multifunctional, chimeric enzymes to deconstruct a complex C5 syrup. Starting from a natural enzyme, she computationally designed and model chimeric variants that were subsequently tested successfully in the lab proving that they were actually incorporating the desirable functionalities.

May

One of our previous articles, Buwchitin: A Ruminal Peptide with Antimicrobial Potential against Enterococcus faecalis " has been included in eBook Antimicrobial (AMPs) and anticancer peptides (ACPs). This Research Topic will bring together research investigating how AMPs and ACPs are being used, functionalised and produced for clinical applications through a collection of original research and reviews. A primary aim is to highlight approaches that are used to improve efficacy of AMPs and ACPs and also draw attention to similarities in approaches and also what approaches work in one area but not in another. It is hoped that this collection of work would provide researchers with a bank of knowledge to aid in the design of AMPs and ACPs to combat the worldwide problem of antibiotic resistance in microbes and in treating cancer and chemotherapeutic-resistant disease.
The eBook is available at or can be downloaded from or here as epub.

2017

February

Congratulations to Stefani who successfully defended her PhD after a four long hours viva examination. Stefani passed her viva on Feb the 6th with just minor corrections. Thus, Dr Dritsa from now on. She is currently working as PostDoc at the University of Kent. The best of luck to you!

2016

December

One more before the end of the year. New publication in The Journal of Molecular Biology. This work describes a novel, sequence-based, prediction method of protein interfaces: iFrag. iFrag represents a novel approach to predict protein interfaces that relies on finding common sequence fragments between pairs of protein sequences exploiting the underlying interologs. iFrag makes no assumptions about protein domain composition, does not use protein structural information and does not need to perform multiple sequence aligments and can even predict small interaction sites consisting only of few residues. Thus, predicted interfaces range from short fragments composed of few residues to domains of proteins, depending on available information on PPIs. Moreover, as a proof of concept iFrag was used to predict peptides sequences that will compete with the aggregation of β-amyloid in Alzheimer's disease; predictions that were subsequently verified by experimental means. This work is the results of our long-term collaboration with Prof Oliva from the Universitat Pompeu Fabra in beautiful Barcelona. We plan to include iFrag in future releases of the InteractoMIX platform. The paper is available at or can be downloaded from .

November

New publication in Nucleus. This work describes a historical overview and insight onto the machinery underpinning chromatin dynamics and the computational structural modeling of such machinery. This work has been done in collaboration with Prof Beato from the Center for Genomic Regulation and Prof Oliva from the Universitat Pompeu Fabra in beautiful Barcelona. The paper is available at or can be downloaded from .

July

Belated welcome to Alexis Amiand from the University of Poitiers who will be with us over the summer as Visiting Student. Alexis joined us on late May this year to work on the development of an automatic system to annotate protein and gene sequences by using on line tools and servers. Also, Alexis is really kind in improving his Bioinformatics and English skill whist enjoying Aberystwyth and the Welsh countryside.

July

Congratulations to Altan Kara. We have a new PhD in da house. Altan passed his viva on July 6th with just minor corrections, thus congratulations and the best of luck!

June

New publication in Biochemistry Society Transations. This work describes a integrated platform: InteractoMIX that includes 11 published tools and databases for the analysis of protein-protein interactions, ranging from the interactome level to their structural details. Thus, the different tools compiled in InteractoMIX facilitates the in silico study of some of the top topics in the current biomedical research in PPIs on a user-friendly and intuitive manner. Both computational and experimental scientists can expand their knowledge on explicit pathways (in which their proteins of interest are involved), identify key residues related to the function of a particular interaction, model the structure of protein complexes and, eventually, predict new therapeutic targets and its corresponding agents including the de novo modeling of orthosteric peptides to target particular PPIs. The paper is available at or can be downloaded from .

May
New publication in Proteins. This paper describes the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. The paper is available at or can be downloaded from .

2015

September
New publication in BMC Bioinformatics. This work describes the implementation of a sequence-based meta-predictor, MetaPred2CS, designed to predict pairing in prokaryots two component systems. The work was carried out by Altan Kara as part of his PhD research. The paper describing the method is available at or can be downloaded from . A web application interfacing the method is available at here.

March
V-D²OCK is now on-line. V-D²OCK is our newest web-application designed to derive structure models based on data-driven docking. V-D²OCK has been published in PlOS One, available at or download from . V-D²OCK is accessible in our servers web-page.

2014

2013

July
We have published a review article in MedChemComm. This review discusses the use of peptides as drug surrogate to interrogate and interfere with protein function. We briefly present our computational approach to model and design orthosteric peptides based on our iMotifs library that will be further discussed in a subsequent publication.

January

We have contributed a chapter devoted to the modular perspective of protein structure and its application in loop modeling in the newly published Protein Supersecondary Structures book edited by Alexander E. Kister , ISBN: 978-1-62703-064-9 (Print) 978-1-62703-065-6 (Online) by SpringerLink. In this work, we discuss recent observations about the saturation of Smotif geometries in protein structures and how it opens new avenues in protein structure modeling and design. As a first application of these observations we describe our loop conformation modeling algorithm, ArchPred that takes advantage of Smotifs classification. In this application, instead of focusing on specific loop properties the method narrows down possible template conformations in other, often not homologous structures, by identifying the most likely supersecondary structure environment that cradles the loop. Beyond identifying the correct starting supersecondary structure geometry, it takes into account information of fit of anchor residues, sterical clashes, match of predicted and observed dihedral angle preferences, and local sequence signal. The chapter was contributed by Narcis Fernandez-Fuentes and Prof. Andras Fiser from Albert Einstein College of Medicine.

2012

May
Paper accepted in Bioinformatics. This paper describes our new method: Multi-VORFFIP; a method to predict functional sites in protein structures. Web-server is accessible here.

March

We have contributed a chapter devoted to computational tools and databases for the study of protein-protein interactions in the newly published book Protein-Protein interactions. Computational and Experimental Tools edited by Weibo Cai and Hao Hong, ISBN 978-953-51-0397-4. The chapter reviews current computational approaches for the study protein-protein interactions, ranging from the prediction of protein complexes, charting of hot spots in protein interface and the prediction of protein-binding sites. You can download a pdf of the chapter here. More information about the book here. The chapter was contributed by Narcis Fernandez-Fuentes, Joan Segura and Jose Ramon Blas from Universidad Castilla La Mancha.

2011

November
Paper accepted in Human Molecular Genetics. This paper describes the characterization of a mutation linked to disease that affects the global eye development. The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. The strcutural modeling of p.E49V mutation shows that it maps onto the helix that recognized the DNA sites, and thus likely to impair the function of ATOH7.Among others research groups, this was a collaboration between Dr. Fernandez-Fuentes and Dr. Mani Ali's group at the Leeds Institute of Molecular Medicine.

October
Paper accepted in Nucleic Acids Research. This paper describes our new database: CAPS-DB; a structural classification of helix capping-motifs. CAPS-DB presents a comprehensive structural classification of helix cappings in protein structures. The classification has been derived using a novel, fast and reliable clustering method that is based in geometry and conformation. The information contained in CAPS-DB has a number of potential applications in the fields of Structural Biology, Protein Design and Engineering an Bioinformatics. Database is accessible here.

September
Paper accepted in The American Journal of Human Genetics. This paper describes the characterization of a mutation linked to an eye disease. Among others research groups, this was a collaboration between Dr. Fernandez-Fuentes and Dr. Mani Ali's group at the Leeds Institute of Molecular Medicine.

August
Paper accepted in BMC Bioinformatics. This paper describes our new method: VORFFIP; a method to predit protein binding sites in protein structures. Web-server is accessible here.

2010

December

We have contributed a chapter devoted to loop modeling techniques in the newly published book Introduction to Protein Structure Prediction edited by Huzefa Rangwala and George Karypis. The book has been published by Wiley as a part of the Wiley Series on Bioinformatics: Computational Techniques and Engineering and presents a quite comprehensive and updated review of techniques in protein structure prediction and its applications. You can take a look (and eventually buy the book) here. The chapter in modeling loops in protein structure was contributed by Dr. Fernandez-Fuentes and Dr. Fiser at the Albert Einstein College of Medicine.

November
Paper accepted in Nucleic Acids Research. This paper describes our new database: PCRPi-DB; a database of annotated hot spots in protein interfaces. PCRPI-DB is weekly updated. Database is accessible here.

October

We got the front page on Nucleic Acids Research on October 2010. The structure describes a computer generated model of the dimeric Runx1 complex bound to two overlapping palindromic Runx1 binding sites. Runx1 normally binds to single Runx1 binding sites as part of a complex of Runx1 plus CBFb that is known as Core Binding Factor (CBF). However, the article by Bowers et al. in this issue demonstrates that Runx1 can also form dimeric complexes where two Runx1 Rel-like domains engage GG motifs on opposite strands of overlapping Runx1 sites. This was a collaborative project between Dr. Fernandez-Fuentes and Prof. Cockerill's lab at the Leeds Institute of Molecular Medicine.

August
Paper accepted in PlOS ONE. This paper describes our new web application PCRPi-W, a web server to chart hot spot in protein structures. Server is accessible here.

June
Paper accepted in Molecular Vision. This paper describes the characterization of a mutation linked to an eye disease. Among others research groups, this was a collaboration between Dr. Fernandez-Fuentes and Dr. Mani Ali's group at the Leeds Institute of Molecular Medicine.

May
Paper accepted in PlOS Genetics. This paper describes the characterization of a gene linked to dilated cardiomyopathy (DCM). This was a collaboration between Dr. Fernandez-Fuentes and Prof. Dear's lab at the Leeds Institute of Molecular Medicine.

April
Paper accepted in Nucleic Acids Research. This paper describes the experimental evidence and structural modeling of RUNX DNA binding domain binding as a dimer and recognizing. two overlapping DNA bindind sites within a palindromic sequence. This was a collaborative project between Dr. Fernandez-Fuentes and Prof. Cockerill's lab at the Leeds Institute of Molecular Medicine.

March
Paper accepted in PLoS Computational Biology. Structural genomics efforts aim at exploring the repertoire of three-dimensional structures of protein molecules. While genome scale sequencing projects have already provided us with all the genes of many organisms, it is the three dimensional shape of gene encoded proteins that defines all the interactions among these components. Understanding the versatility and, ultimately, the role of all possible molecular shapes in the cell is a necessary step toward understanding how organisms function. In this work we explored the rules that identify certain shapes as novel compared to all already known structures. The findings of this work provide possible insights into the rules that can be used in future works to identify or design new molecular shapes or to relate folds with each other in a quantitative manner. This was a collaborative project between Dr. Fernandez-Fuentes and Dr Fiser's lab at the Albert Einstein College of Medicine.

2009

November
Paper accepted in Nucleic Acids Research. This paper describe a new computational method: PCRPi, Presaging Critical Residues in Protein interfaces. PCRPi depends on the integration of diverse metrics into an unique probabilistic framework by using Bayesian networks. PCRPi have benchmarked using a large set of experimentally verified hot spot and on a blind prediction on the protein complex formed by HRAS protein and single domain antibody. Under both scenarios, PCRPi delivered consistent and accurate prediction. Moreover, PCRPi is a robust predictor that is able to handle cases where some of the input data is either missing or highly noisy (e.g. evolutionary information). The PCRPi work has mainly been carried out by Dr. Assi with the collaboration of Prof. T.H. Rabbitts' group

September
New paper in Human Molecular Genetics . This article explore the effect of mutations in the assembly of NAP57-SHQ1 ribonucleoprotein complex and its relationship with Dyskeratosis congenita. Mutations concentrate in the N- and C-termini of NAP57 but not in its central catalytic domain raising questions as to their impact. We demonstrate that the N- and C-termini together form the binding surface for the H/ACA RNP assembly factor SHQ1 and that dyskeratosis congenita mutations modulate the interaction between the two proteins. This was a collaborative project between Dr. Fernandez-Fuentes' previous lab, Dr Fiser's lab and Dr. Meier's lab at the Albert Einstein College of Medicine. This is yet one more example of a wet-dry lab combined approach to address important questions in Biology.

January
New paper in Fronteirs of Bioscience . This article explores the biophysical character of HPV E2 viral proteins with the goal of identifying characteristics that associated with risk of virally caused malignancy. The amino acid sequence, 3D structure and electrostatic features of the E2 protein DNA binding domain are highly conserved; specific interactions with DNA binding sites have also been conserved. In contrast, the E2 protein's transactivation domain does not have extensive surfaces of highly conserved residues. Rather, regions of high conservation are localized to small surface patches.