Article
Biochemistry & Molecular Biology
Vijay Kumar
Summary: The hexanucleotide repeat expansion in C9orf72 is a major cause of ALS and FTD, and the protein complex formed by C9orf72, SMCR8, and WDR41 plays a crucial role in regulating cellular processes like autophagy and membrane trafficking. Recent cryo-EM structure studies have provided insights into the structure-function relationship of C9orf72, while local frustration analysis revealed important structural features of the C9orf72-SMCR8 complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shafiul Haque, Pawan Kumar, Darin Mansor Mathkor, Farkad Bantun, Naif A. Jalal, Ahmad Hasan Mufti, Amresh Prakash, Vijay Kumar
Summary: This study aims to investigate the binding of antiviral compounds with SARS-CoV-2 nucleocapsid protein through computational simulations. The results showed that several drugs interacted with RNA binding sites and protein interfaces with high binding energy. These findings provide insights for further validation of the efficacy of these drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Giulia Paiardi, Stefan Richter, Pasqua Oreste, Chiara Urbinati, Marco Rusnati, Rebecca C. Wade
Summary: Heparin has been found to have antiviral activity against SARS-CoV-2 by inhibiting viral binding to host cells, competing with binding to host heparan sulfate proteoglycan coreceptors, and preventing spike cleavage. These findings provide insights into potential strategies for SARS-CoV-2 antiviral therapy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Shafiul Haque, Fatima Khatoon, Sami S. Ashgar, Hani Faidah, Farkad Bantun, Naif A. Jalal, Fadi S. I. Qashqari, Vijay Kumar
Summary: The N protein of SARS-CoV-2 is a mutational hotspot and mutations in this protein may increase viral transmissibility and virulence. A study found that 11 mutations in N protein may cause deleterious effects on protein stability and function. By altering energetics and residual frustration, these mutations might affect the stability, function, and pathogenicity of SARS-CoV-2.
BIOTECHNOLOGY AND GENETIC ENGINEERING REVIEWS
(2023)
Article
Plant Sciences
Shaofang Li, Chenyang Wang, Chenjiang You, Xueping Zhou, Huanbin Zhou
Summary: T-LOC is a robust approach for studying T-DNA integration sites (TISs) in transgenic plants, independent of the integration pattern. It can recover all types of TISs and characterize the genomic changes at the integration sites. T-LOC utilizes whole-genome sequencing data to accurately locate and characterize TISs, and has been validated using various sequencing methods.
Article
Multidisciplinary Sciences
Ryan P. Hildebrandt, Kathryn R. Moss, Aleksandra Janusz-Kaminska, Luke A. Knudson, Lance T. Denes, Tanvi Saxena, Devi Prasad Boggupalli, Zhuangyue Li, Kun Lin, Gary J. Bassell, Eric T. Wang
Summary: RNA binding proteins (RBPs) are important facilitators of spatially regulated gene expression. Muscleblind-like (MBNL) proteins, implicated in myotonic dystrophy and cancer, localize RNAs to myoblast membranes and neurites through unknown mechanisms. The researchers discovered that MBNL forms motile and anchored granules in neurons and myoblasts and selectively associates with kinesins Kif1b alpha and Kif1c through its zinc finger (ZnF) domains. Other RBPs with similar ZnFs also associate with these kinesins, suggesting a motor-RBP specificity code. The perturbation of MBNL and kinesins leads to widespread mRNA mis-localization, including depletion of Nucleolin transcripts from neurites. The study also establishes general strategies for studying multi-functional, modular domains of RBPs.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Romain Magnez, Christian Bailly, Xavier Thuru
Summary: This review highlights the crucial roles of protein-protein interactions (PPIs) in life processes and their involvement in various human diseases. It introduces Microscale Thermophoresis (MST) as a rapid, robust, and efficient alternative method for detecting therapeutically pertinent proteins. The review summarizes selected case studies and discusses the benefits and limitations of MST in studying PPIs and identifying regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Jim Warwicker
Summary: pH sensitivity plays a crucial role in biology and efforts have been made to establish physical models that can rationalize and predict pH dependence based on molecular structures. Accurate calculation of ionizable group solvation and hydration, as well as modeling of relevant conformations, are key challenges. Explicit solvent methods coupled with molecular dynamics simulation are complementing implicit solvent techniques, but high-throughput modeling is still necessary for large-scale biological data acquisition. Furthermore, the consideration of pH sensors beyond histidine side chains and the incorporation of other concepts from bioinformatics can enhance modeling. In addition, the inclusion of multiple experimental structures helps mitigate small conformational variations and analyze larger functional changes. These aspects are demonstrated by new research on the pH dependence of variants of the spike protein in SARS-CoV-2, including the prediction of a shift in the balance of locked, closed, and open forms for the Omicron variant spike protein at neutral pH.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Vanessa R. Lobo, Jim Warwicker
Summary: The transition between receptor binding domain (RBD) up and down forms of the SARS-CoV-2 spike protein trimer is coupled to receptor binding and pH, with acidic sidechains becoming buried in the locked form at lower pH. This model suggests that replacing these acidic sidechains could stabilize spike protein trimers and improve recovery at neutral pH, offering an alternative method for stabilizing spike proteins with implications for vaccine design.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemical Research Methods
Jim Warwicker
Summary: This study explored the stability of spike proteins from SARS-CoV-2 and other coronaviruses under different conditions, identifying key residues that may affect their pH-dependence. These findings provide new insights into the infection mechanism and mutations of SARS-CoV-2.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Cyril Planchais, Alejandra Reyes-Ruiz, Robin Lacombe, Alessandra Zarantonello, Maxime Lecerf, Margot Revel, Lubka T. Roumenina, Boris P. Atanasov, Hugo Mouquet, Jordan D. Dimitrov
Summary: This study revealed a reshaping of the physicochemical characteristics in the interaction between SARS-CoV-2 variants and ACE2, shedding light on the implications for viral tropism and evasion of immune responses during evolution.
Article
Biochemistry & Molecular Biology
Cyril Planchais, Alejandra Reyes-Ruiz, Robin Lacombe, Alessandra Zarantonello, Maxime Lecerf, Margot Revel, Lubka T. Roumenina, Boris P. Atanasov, Hugo Mouquet, Jordan D. Dimitrov
Summary: This study investigates the molecular interaction between S proteins of SARS-CoV-2 variants and ACE2 receptor, and how this interaction has evolved during the pandemic. It reveals a profound remodeling of the physicochemical characteristics of the interaction during evolution, with Omicron RBD exhibiting unique conformational dynamics and non-covalent forces compared to other variants. The study also explores the impact of these changes on the binding specificity of S proteins and their recognition of unrelated human proteins.
Article
Computer Science, Artificial Intelligence
Umer Rashid, Aiman Javid, Abdur Rehman Khan, Leo Liu, Adeel Ahmed, Osman Khalid, Khalid Saleem, Shaista Meraj, Uzair Iqbal, Raheel Nawaz
Summary: This research provides an automated solution for addressing oral health issues by implementing deep learning methods and software tools to localize and present carious regions in dental images. The evaluations by dentists demonstrate high accuracy and overall satisfaction with the proposed system.
PEERJ COMPUTER SCIENCE
(2022)
Article
Multidisciplinary Sciences
Joy Edwards-Hicks, Huizhong Su, Maurizio Mangolini, Kubra K. Yoneten, Jimi Wills, Giovanny Rodriguez-Blanco, Christine Young, Kevin Cho, Heather Barker, Morwenna Muir, Ania Naila Guerrieri, Xue-Feng Li, Rachel White, Piotr Manasterski, Elena Mandrou, Karen Wills, Jingyu Chen, Emily Abraham, Kianoosh Sateri, Bin-Zhi Qian, Peter Bankhead, Mark Arends, Noor Gammoh, Alex von Kriegsheim, Gary J. Patti, Andrew H. Sims, Juan Carlos Acosta, Valerie Brunton, Kamil R. Kranc, Maria Christophorou, Erika L. Pearce, Ingo Ringshausen, Andrew J. Finch
Summary: MYC activation enhances global transcription and translation, creating a metabolic demand. Glutamine limitation leads to an imbalance of metabolic supply and demand, sensitising cells to apoptosis. Glutamine supports the viability of MYC-overexpressing cells through TCA cycle energetics rather than biosynthetic mechanism.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Athanassios C. Tsipis, Constantinos A. Tsipis
Summary: This study investigates the anomeric and Perlin effects in 2-substituted-2-fluorotetrahydro-2H-pyrans using sensitive structural, energetic, and NMR probes. Different substituents display preferences for axial or equatorial conformations, with some inducing normal Perlin effects and others the reverse. The research demonstrates a general relationship and shared stereoelectronic origin between the Perlin and anomeric effects.
JOURNAL OF PHYSICAL CHEMISTRY A
(2021)
Article
Chemistry, Physical
Jia-Liang Shen, Min-Yeh Tsai, Nicholas P. Schafer, Peter G. Wolynes
Summary: Protein aggregation plays a crucial role in determining the structure of membraneless organelles and the pathogenesis of diseases, but the diverse types of aggregates and inherent stochastic nature present challenges to theoretical and computational modeling. Introducing a new approach to model stochastic aggregation kinetics, which incorporates noise into averaged equations, helps to explore aggregation mechanisms and statistics more efficiently. The second stochasticization scheme reveals a scaling law that correlates fluctuations in aggregate size with the total number of monomers, demonstrating the value of bridging the gap between in vivo cell biology and detailed modeling.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Review
Chemistry, Multidisciplinary
Stefano Gianni, Maria Ines Freiberger, Per Jemth, Diego U. Ferreiro, Peter G. Wolynes, Monika Fuxreiter
Summary: Proteins and their complexes can be described as ensembles that populate an energy landscape, where the diversity arises from the conflicts between interactions shaping the energy landscape. Within this framework, alternative sets of suboptimal contacts can encode specificity without achieving a single structural optimum. The interplay between frustration and fuzziness offers insights into the structural and dynamical continuum of protein assemblies.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Physical
Maria Freiberger, Peter G. Wolynes, Diego U. Ferreiro, Monika Fuxreiter
Summary: The study reveals that complexes of disordered proteins exhibit a high degree of local frustration, especially at the binding interface, leading to multiple bound substates with distinct frustration patterns, differently populated in complexes with different partners. This explains how specificity of disordered proteins can be achieved without a single common bound conformation and how the conflict between different interactions can be used to control the binding to multiple partners.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemical Research Methods
Atilio O. Rausch, Maria Freiberger, Cesar O. Leonetti, Diego M. Luna, Leandro G. Radusky, Peter G. Wolynes, Diego U. Ferreiro, R. Gonzalo Parra
Summary: The study introduces a software package called FrustratometeR, which can easily compute local energetic frustration in natural proteins, facilitating the analysis of protein structure and function.
Article
Biochemistry & Molecular Biology
Yuan-Wei Ma, Tong-You Lin, Min-Yeh Tsai
Summary: This study investigates the free energy landscape of a free Abeta monomer binding to an existing fibrillar surface using molecular dynamics simulations, revealing three stages of surface-dependent events. Additionally, by identifying peptide precursors and studying their heterogeneity, researchers found a correlation between surface heterogeneity and energy frustration of specific residues.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biophysics
Xun Chen, Wei Lu, Min-Yeh Tsai, Shikai Jin, Peter G. Wolynes
Summary: This study computationally explores the role of heme in protein folding and structure, using a hybrid model and carefully designed force fields. The results show that different types of hemes can improve protein structure predictions and stabilize the folded state.
JOURNAL OF BIOLOGICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Xun Chen, Min-Yeh Tsai, Peter G. Wolynes
Summary: Accurate reading of genetic information during transcription is crucial for gene expression. Proteins can recognize DNA sequences through direct readout (specific interactions between amino acid residues and nucleotide bases) or indirect readout (DNA sequence elements cooperating to localize transcription factors). In this study, a protein-DNA model is used to investigate the sequence specificity of the binding of PU.1 protein to DNA. It is found that the binding specificity of PU.1 is achieved through a nonspecific electrostatically driven DNA mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Mihaly Varadi, Stephen Anyango, David Armstrong, John Berrisford, Preeti Choudhary, Mandar Deshpande, Nurul Nadzirin, Sreenath S. Nair, Lukas Pravda, Ahsan Tanweer, Bissan Al-Lazikani, Claudia Andreini, Geoffrey J. Barton, David Bednar, Karel Berka, Tom Blundell, Kelly P. Brock, Jose Maria Carazo, Jiri Damborsky, Alessia David, Sucharita Dey, Roland Dunbrack, Juan Fernandez Recio, Franca Fraternali, Toby Gibson, Manuela Helmer-Citterich, David Hoksza, Thomas Hopf, David Jakubec, Natarajan Kannan, Radoslav Krivak, Manjeet Kumar, Emmanuel D. Levy, Nir London, Jose Ramon Macias, Madhusudhan M. Srivatsan, Debora S. Marks, Lennart Martens, Stuart A. McGowan, Jake E. McGreig, Vivek Modi, R. Gonzalo Parra, Gerardo Pepe, Damiano Piovesan, Jaime Prilusky, Valeria Putignano, Leandro G. Radusky, Pathmanaban Ramasamy, Atilio O. Rausch, Nathalie Reuter, Luis A. Rodriguez, Nathan J. Rollins, Antonio Rosato, Luis Serrano, Gulzar Singh, Petr Skoda, Carlos Oscar S. Sorzano, Jan Stourac, Joanna Sulkowska, Radka Svobodova, Natalia Tichshenko, Silvio C. E. Tosatto, Wim Vranken, Mark N. Wass, Dandan Xue, Daniel Zaidman, Janet Thornton, Michael Sternberg, Christine Orengo, Sameer Velankar
Summary: PDBe-KB is an open collaboration platform that aims to integrate functional and biophysical annotations from world-leading specialist data resources, serving the Protein Data Bank. By developing standardized data exchange formats and integrating functional annotations from partner resources, PDBe-KB aims to place macromolecular structure data in a biological context and provide valuable biological insights.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Xinyu Gu, Nicholas P. Schafer, Peter G. Wolynes
Summary: This paper discusses the mechanism of translational control of messenger RNA through RNA-binding proteins, explores the role of prions in locally controlling translation in dendritic spines, and the factors influencing translation in different structured mRNA/protein aggregates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Yana Bromberg, Ariel A. Aptekmann, Yannick Mahlich, Linda Cook, Stefan Senn, Maximillian Miller, Vikas Nanda, Diego U. Ferreiro, Paul G. Falkowski
Summary: Biological redox reactions are driven by enzymes with similar structural geometry and amino acid sequences, reflecting the availability of key transition metals over geological time. The earliest biologically functional peptides may have existed before the assembly of fully functional protein domains over 3.8 billion years ago.
Article
Biochemical Research Methods
A. A. Aptekmann, J. Buongiorno, D. Giovannelli, M. Glamoclija, D. U. Ferreiro, Y. Bromberg
Summary: Metal-binding proteins play a central role in maintaining life processes, but experimental annotation is lacking and computational techniques are often imprecise. In this study, we developed a machine learning-based method, mebipred, which accurately identifies metal-binding proteins and annotates metal ions. Mebipred can also identify metal-binding capabilities from short sequence stretches, making it useful for metagenomic samples. Analysis of microbiome data revealed different metal preferences and the impact of ion concentration changes on metal-binding protein abundance.
Article
Biochemistry & Molecular Biology
Pablo Galaz-Davison, Diego U. Ferreiro, Cesar A. Ramirez-Sarmiento
Summary: This study used publicly available genomic RfaH protein sequences to construct a complete multiple sequence alignment and predicted their secondary structures. Coevolutionary analysis revealed the structural interconversion and key interactions of RfaH, shedding light on the action of this metamorphic protein.
Article
Multidisciplinary Sciences
Ezequiel A. Galpern, Jacopo Marchi, Thierry Mora, Aleksandra M. Walczak, Diego U. Ferreiro
Summary: Repeat proteins, made up of tandem copies of similar amino acid stretches, have diverse folding mechanisms that can be predicted from sequence scores.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Physical
Ignacio E. Sanchez, Ezequiel A. Galpern, Martin M. Garibaldi, Diego U. Ferreiro
Summary: In this study, molecular information theory is applied to analyze the folding of single domain proteins. The average information contained in evolved protein sequences was found to be very close to the average information needed for folding. The effective alphabet size in evolved proteins is around 5 and the energy-to-information conversion efficiency is approximately 50%.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Tong-You Lin, Yuan-Wei Ma, Min-Yeh Tsai
Summary: Proline cis/trans isomerization controls protein local conformational changes through its mechanical rigidity. The molecular mechanism of proline's amyloid-disrupting capacity remains unclear. This study investigates the influence of proline residues in polypeptide chains on amyloid propensity using simulated aggregation processes. The results reveal that proline variants can influence the formation of ordered oligomers, leading to distinct amyloid formation pathways.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
