Article
Biochemistry & Molecular Biology
Deborah Giordano, Cassiano Langini, Amedeo Caflisch, Anna Marabotti, Angelo Facchiano
Summary: The study compares the structures and flexibility of transglutaminase enzymes from Kutzneria albida (KalbTGase) and Streptomyces mobaraensis (MTGase). It is found that KalbTGase is more rigid and has a more closed catalytic site at room temperature, indicating higher selectivity compared to MTGase. Preliminary results at higher temperature suggest enhanced flexibility of KalbTGase, potentially allowing it to adapt to different substrates, while MTGase shows reduced adaptability and catalytic activity at higher temperatures.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Mirjana M. Maljkovic, Nenad S. Mitic, Alexandre G. de Brevern
Summary: This study focuses on predicting Protein Blocks (PBs) from amino acid sequences using different data mining approaches and machine learning algorithms. The constructed models show varying importance of input attributes among algorithms. Utilizing information about amino acids in intrinsically disordered regions and repeats can improve the prediction accuracy for some PBs.
Article
Multidisciplinary Sciences
Shaun M. Kandathil, Joe G. Greener, Andy M. Lau, David T. Jones
Summary: The study presents a deep learning-based method for predicting protein structure, which reduces preprocessing time and directly outputs main chain coordinates. The approach is fast, easy to use, and produces accurate structural models. It enables large-scale modeling of proteins on minimal hardware.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Barry J. Grant, Lars Skjaerven, Xin-Qiu Yao
Summary: Bio3D is a set of R packages for analyzing biomolecular sequences, structures, and dynamics, with recent developments including segregation into separate packages and introduction of a new method called ensemble difference distance matrix analysis (eDDM). The eDDM approach helps identify residue-wise determinants underlying specific functional processes by calculating and comparing atomic distance matrices across large sets of homologous structures.
Article
Biochemistry & Molecular Biology
Yann Vander Meersche, Gabriel Cretin, Alexandre G. de Brevern, Jean-Christophe Gelly, Tatiana Galochkina
Summary: Understanding protein flexibility is crucial for studying important molecular mechanisms. MEDUSA, a Deep Learning based tool, uses evolutionary information and amino acid properties to predict flexibility in protein sequences, providing valuable insights into protein dynamics.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemical Research Methods
Varun Ullanat, Nikhil Kasukurthi, Shruthi Viswanath
Summary: This study aims to address the issue of varying precision in different regions of an integrative model due to varying input information. The researchers developed a method called PrISM to efficiently identify high- and low-precision regions in integrative models.
Article
Biochemistry & Molecular Biology
Charles Christoffer, Vijay Bharadwaj, Ryan Luu, Daisuke Kihara
Summary: Protein-protein docking is a useful tool for modeling protein complex structures and understanding their functional mechanisms. Despite the increasing number of known protein structures, there are still cases where the structures of proteins for docking are unknown. This study integrated the AttentiveDist method for protein structure prediction into the LZerD docking webserver, allowing users to submit protein sequences and obtain full-complex atomic models without providing any structure themselves.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Medicinal
Francini Fonseca Lopez, Jiayuan Miao, Jovan Damjanovic, Luca Bischof, Michael B. Braun, Yingjie Ling, Marcus D. Hartmann, Yu-Shan Lin, Joshua A. Kritzer
Summary: The Nrf2 transcription factor regulates the response to oxidative stress, and Keap1 is its main negative regulator. This study used molecular dynamics simulations to predict the preorganization of cyclic peptides and correlated it with binding affinities for Keap1. The findings provide insights into designing selective inhibitors of protein-protein interactions using cyclic peptides.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Fabian Barthels, Tanja Schirmeister, Christian Kersten
Summary: The study utilizes B-factor analysis of X-ray protein structures to provide a new tool and method for structure-based drug design. By analyzing crystallographic protein-ligand complexes, important references are provided for further drug optimization.
MOLECULAR INFORMATICS
(2021)
Article
Biochemical Research Methods
Dominik Schwarz, Guy Georges, Sebastian Kelm, Jiye Shi, Anna Vangone, Charlotte M. Deane
Summary: Co-evolution analysis and machine-learning techniques have improved the accuracy of predicting residue-residue contacts and distances in protein structures. The shape of predicted distance distributions contains information on the rigidity or flexibility of a protein and its constituent residues.
Review
Biochemistry & Molecular Biology
Serena Rosignoli, Alessandro Paiardini
Summary: The field of structural bioinformatics has seen an exponential growth in available tools and software, with PyMOL emerging as a key player in providing an open platform for expert knowledge implementation and supporting structural bioinformatics analyses.
Article
Chemistry, Multidisciplinary
Z. Faidon Brotzakis, Philip R. Lindstedt, Ross J. Taylor, Dillon J. Rinauro, Nicholas C. T. Gallagher, Goncalo J. L. Bernardes, Michele Vendruscolo
Summary: By studying the structure and dynamics of the tau-microtubule complex, we identified the ground state and excited states of the complex, as well as important positions for stability. This analysis revealed the destabilizing effects of phosphorylation and acetylation events on the complex, showcasing how determining ground and excited states can uncover functional and regulatory mechanisms of macromolecular complexes.
ACS CENTRAL SCIENCE
(2021)
Article
Cell Biology
Jose Antonio Sanchez Milan, Maria Fernandez-Rhodes, Xue Guo, Maria Mulet, SoFong Cam Ngan, Ranjith Iyappan, Maryam Katoueezadeh, Siu Kwan Sze, Aida Serra, Xavier Gallart-Palau
Summary: This study provides a comprehensive analysis of the impact of oxidative stress and phosphorylation on the aging process. The results show that trioxidized cysteine residues accumulate in the aging proteome and interact with enzymes involved in phosphorylation signaling, altering their structures in a similar way to phosphorylated serine residues. These findings are significant for understanding the interplay between oxidative stress and phosphorylation in aging, and open new avenues for research on protein modifications in chronic diseases and aging.
Review
Biochemical Research Methods
Ammu Prasanna Kumar, Chandra S. Verma, Suryani Lukman
Summary: Rab proteins play a critical role in various diseases, and researchers have proposed a workflow involving multiple computational methods to aid future research in drug discovery targeting Rab protein allosteric sites.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Chemistry, Multidisciplinary
Giuseppina La Sala, Christopher Pfleger, Helena Kack, Lisa Wissler, Philip Nevin, Kerstin Bohm, Jon Paul Janet, Marianne Schimpl, Christopher J. Stubbs, Marco De Vivo, Christian Tyrchan, Anders Hogner, Holger Gohlke, Andrey I. Frolov
Summary: This study developed a structure-based three-parameter model that integrates local binding site information, coevolution information, and information on dynamic allostery to identify potentially hidden allosteric sites in ensembles of protein structures. The model successfully ranked all known allosteric pockets in the top three positions when tested on five allosteric proteins. Additionally, two novel druggable sites were identified and confirmed in MAT2A and BCKDK protein structures. This model can be used in drug discovery to identify allosteric pockets.
Article
Cell Biology
Nora El Jahrani, Gabriel Cretin, Alexandre G. de Brevern
Summary: Essential thrombocythemia (ET) is defined by a significant increase in platelet numbers and a quarter of patients with ET have mutations in the CALR gene. This study compiled 155 different CALR variants, redefining 5 new classes and extending the classification of type 1-like and type 2-like. The analysis revealed a class of CALR variants not associated with ET, while showing common features among CALR variants associated with ET.
Article
Cell Biology
M. Y. Koker, N. Sarper, C. Albayrak, B. Zulfikar, E. Zengin, B. Saraymen, D. Albayrak, B. Koc, H. Avcilar, M. Karakukcu, C. Chenet, F. Bianchi, A. G. de Brevern, R. Petermann, V Jallu
Summary: This study reported platelet phenotypes and allelic variations in 28 Turkish GT patients, and investigated the effects of different variants on alpha IIb beta 3 expression using transfected cell lines. New alleles were described, and it was suggested that some variations might be new causes of GT.
Article
Biochemistry & Molecular Biology
Jade Fogha, Alexandre G. de Brevern, Julien Diharce
Summary: Protein-protein interactions (PPIs) are important in biological processes and pathologies. This study used molecular dynamics simulations and binding energy calculations to evaluate the interactions between IL-3 and IL-3R alpha. The results revealed different conformations and interaction profiles in the wild-type and mutant complexes, providing new information for drug discovery.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Hematology
Aline Floch, Christine Lomas-Francis, Sunitha Vege, Anna Burgos, Roser Hoffman, Robin Cusick, Alexandre G. de Brevern, Connie M. Westhoff
Summary: This study investigated ERMAP in individuals who made antibodies to high prevalence Scianna antigens and proposed a 3D model to locate the residues associated with known antigens. Two new SC alleles were identified, and the extracellular location of Scianna residues responsible for antigen expression was confirmed.
Article
Hematology
Aline Floch, Christine Lomas-Francis, Sunitha Vege, Steven Brennan, Gayane Shakarian, Alexandre G. de Brevern, Connie M. Westhoff
Summary: A novel Lutheran antigen was identified and a updated BCAM 3D model was proposed. The study found that the c.212G > A change resulted in the loss of LUGA (LU24) antigen. This model and the discovery that nearly all residues associated with the expression of a Lutheran antigen are exposed will help evaluate the significance of new polymorphisms.
Article
Hematology
Cedric Vrignaud, Mahmoud Mikdar, Romain Duval, Luc Reininger, Vijaya L. Damaraju, Michael Sawyer, Yves Colin, Caroline Le Van Kim, Jean-Christophe Gelly, Catherine Etchebest, Thierry Peyrard, Slim Azouzi
Summary: This study identified a novel high-prevalence antigen, AUG4, in the Augustine blood group system, which is encoded by the rare SLC29A1 variant allele AUG*04 (c.242A > G, p.Asn81Ser). The study provides insights into the molecular structure and potential pathogenic mechanisms of this antigen.
Article
Biochemistry & Molecular Biology
Alexandre G. de Brevern
Summary: Knowledge of the 3D structure of proteins is crucial but challenging to obtain due to high costs and experimental difficulties. The introduction of AlphaFold Deep Learning approach has revolutionized the field, allowing analysis of large amounts of data for evaluating results. By analyzing the 3D human proteome, this study identifies certain local conformations that may be inaccurately predicted and suggests potential areas for improvement.
Article
Biochemistry & Molecular Biology
Akhila Melarkode Vattekatte, Julien Diharce, Joseph Rebehmed, Frederic Cadet, Fabrice Gardebien, Catherine Etchebest, Alexandre G. de Brevern
Summary: Conformational flexibility is crucial for the functional and structural stability of antibodies, and it determines the strength of antigen-antibody interactions. Camelidae express a unique subtype of antibody called Heavy Chain only Antibody, which has excellent solubility and stability. Molecular dynamics simulations of a large number of non-redundant VHH structures were performed for the first time, revealing the prevalent movements and changes in flexibility in different regions of VHH. This study provides insights into the design of VHH and their flexibility in different regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Aravindan Arun Nadaradjane, Julien Diharce, Joseph Rebehmed, Frederic Cadet, Fabrice Gardebien, Jean-Christophe Gelly, Catherine Etchebest, Alexandre G. de Brevern
Summary: Heavy Chain Only Antibodies are specific to Camelid species and their heavy chain variable domain (VHH) holds promise for research and therapy. However, due to limited experimental structures, structural model prediction for VHH is necessary. This study assesses and compares the quality of predictions from various modelling methodologies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Ragousandirane Radjasandirane, Alexandre G. de Brevern
Summary: Essential thrombocythemia (ET) is a blood cancer characterized by platelet overproduction. CALR mutations are found in 25-30% of ET patients, and JAK2, MPL, or CALR proteins may be involved in platelet overproduction. CALR variants are classified into five classes, with A and B being the most common in ET patients. Molecular dynamics simulations were used to analyze the structural dynamics of these five classes. The results suggest that the newly formed disulfide bond in classes A, B, and C may play an essential role in the pathogenicity of these variants, while class E is unrelated to ET and represents human polymorphisms.
Article
Biochemistry & Molecular Biology
Agata Kranjc, Tarun Jairaj Narwani, Sophie S. Abby, Alexandre G. de Brevern
Summary: In this study, the computationally modeled structure of the host's Duffy antigen/receptor for chemokines (DARC) N-terminal extracellular domain (ECD1) was analyzed using simulations. The results showed that ECD1 remains in a disordered state but contains globular local conformations. This structural information will contribute to a better understanding of the mechanisms underlying Plasmodium vivax malaria infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Carla Martins, Julien Diharce, Aravindan Arun Nadaradjane, Alexandre G. de Brevern
Summary: Camelids have unique antibody structures with independent heavy-chain domain called VHH. V(H)Hs have attracted attention due to their small size and retained properties. However, humanization is required before their use in humans due to their origin in camelids. A tool called Llamanade has been made available for scientific research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Boris Schnider, Yacine M'Rad, Jalaa el Ahmadie, Alexandre G. de Brevern, Anne Imberty, Frederique Lisacek
Summary: The UniLectin portal is a website that centralizes curated and predicted data on lectins and provides support for the study of lectomes. The latest update includes new modules and details our knowledge of the human lectome, featuring 215 unevenly characterized lectins, with a focus on structural information.
NUCLEIC ACIDS RESEARCH
(2023)
Editorial Material
Genetics & Heredity
Olga Valenzuela, Francisco Ortuno, Alfredo Benso, Jean-Marc Schwartz, Alexandre G. de Brevern, Ignacio Rojas
Article
Multidisciplinary Sciences
Samia Aci-Seche, Stephane Bourg, Pascal Bonnet, Joseph Rebehmed, Alexandre G. de Brevern, Julien Diharce
Summary: Computational approaches, especially molecular docking, are widely used in drug discovery projects. However, the availability and reproducibility of the data obtained from these studies have been a concern in the scientific community. This article proposes guidelines for conducting virtual screening experiments and discusses the current state of sharing molecular docking data. The authors also present prospects for enhancing data sharing in docking experiments in the foreseeable future.