Article
Biochemistry & Molecular Biology
Castrense Savojardo, Matteo Manfredi, Pier Luigi Martelli, Rita Casadio
Summary: Solvent accessibility is a key feature in determining protein folding and stability, with disease associated single-residue variations (SRVs) targeting buried residues more frequently than exposed ones. Certain residue types such as glycine, tryptophan, tyrosine, and cysteine are more commonly associated with disease, and the pathogenicity of variations is often linked to the buried nature of the residue.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Balint Biro, Bi Zhao, Lukasz Kurgan
Summary: This study explores the complementarity of different prediction methods, finding that combining structure-trained and disorder-trained predictions leads to improved quality, and demonstrating that predictions accurately reflect various relationships in experimental data.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Biochemical Research Methods
Md Solayman, Thomas Litfin, Jaswinder Singh, Kuldip Paliwal, Yaoqi Zhou, Jian Zhan
Summary: Characterizing RNA structures and functions has traditionally focused on 2D secondary and 3D tertiary structures. However, recent advancements in understanding RNA solvent accessibility as a 1D representation highlight its importance in exploring complex structure-function relationships of RNAs.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemical Research Methods
Gregor Urban, Christophe N. Magnan, Pierre Baldi
Summary: Accurate prediction of protein secondary structure and solvent accessibility is crucial for studying protein evolution, structure, and predicting 3D protein structure. This study presents an improved version of SSpro/ACCpro predictors that utilize deep learning and enhanced features to achieve higher accuracy compared to previous versions.
Article
Biochemistry & Molecular Biology
Alexey V. V. Onufriev
Summary: The stability of protein-ligand complexes is sensitive to the pH of their environment. By computationally examining a set of protein-nucleic acid complexes, including the nucleosome, we found that an increase in intracellular/intra-nuclear pH destabilizes most complexes. We propose the use of ΔΔG(0.3) to quantify the effect, which represents the change in the binding free energy due to a pH increase of 0.3 units.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Ming Lei, Cynthia Quan, John. Y. Wang, Yung-Hsiang Kao, Christian Schoneich
Summary: The study revealed that under light conditions, His molecules can form light-induced His adducts with photooxidized His residues. The presence of PS-20 in commonly used protein drug formulations can significantly elevate the levels of light-induced His-adducts.
PHARMACEUTICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Teng-Ruei Chen, Chia-Hua Lo, Sheng-Hung Juan, Wei-Cheng Lo
Summary: This study found that sequence homology has little effect on the accuracy of protein secondary structure prediction, while redundancy within datasets may lead to overestimation of accuracy. As a result, a rigorous procedure for developing SSP algorithms and making reliable evaluations was proposed to improve future SSP methods.
Article
Biochemistry & Molecular Biology
Matteo Manfredi, Castrense Savojardo, Pier Luigi Martelli, Rita Casadio
Summary: This study introduces a web server that integrates knowledge of solvent and non-solvent exposure with residue conservation, flexibility, and disorder to better understand relevant regions for protein integrity. DeepREx, a deep learning-based tool, classifies residues as buried or exposed and performs at the state-of-the-art in the field. The web server, DeepREx-WS, supplements DeepREx predictions with additional features for characterizing exposed and buried regions, aiding in the identification of residues for variation in protein surface engineering.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Castrense Savojardo, Giulia Babbi, Pier Luigi Martelli, Rita Casadio
Summary: Human genome resequencing projects provide detailed data on single-nucleotide variations in protein-coding regions, many of which are linked to genetic diseases. However, understanding the molecular mechanisms behind these diseases is still limited. This study aims to identify Pfam domains statistically associated with disease-related variations, using 2,513 human protein sequences and 22,763 disease-related variations. The study finds that Pfam models can serve as specific markers to bridge genes, diseases, and disease classes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemical Research Methods
L. F. Signorini, T. Almozlino, R. Sharan
Summary: ANAT3.0 is a powerful Cytoscape plugin that offers updated PPI network databases and a new machine-learning layer to better reconstruct known signaling pathways.
BMC BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Reito Nakamura, Ikumi Tomizawa, Atsushi Iwai, Tetsuo Ikeda, Kota Hirayama, Yung Wen Chiu, Takanobu Suzuki, Airi Tarutani, Tatsuo Mano, Atsushi Iwata, Tatsushi Toda, Youhei Sohma, Motomu Kanai, Yukiko Hori, Taisuke Tomita
Summary: Aggregation of alpha-synuclein into amyloid is a pathological hallmark of neurodegenerative disorders, and inhibiting this aggregation can be a potential therapeutic strategy. This study demonstrates that photo-oxygenation using a photocatalyst successfully inhibits alpha-synuclein aggregation by reducing its seeding ability. The oxidation of histidine residue in alpha-synuclein is found to be responsible for this inhibitory effect.
Article
Biochemistry & Molecular Biology
Alex J. Guseman, Matthew J. Whitley, Jeremy J. Gonzalez, Nityam Rathi, Mikayla Ambarian, Angela M. Gronenborn
Summary: Research shows that introducing single Asp residues on the surface of γD-crystallin by deamidation is unlikely to drive cataract formation in the eye lens.
Article
Biochemistry & Molecular Biology
Silvia Benevenuta, Giovanni Birolo, Tiziana Sanavia, Emidio Capriotti, Piero Fariselli
Summary: An open challenge in computational and experimental biology is to understand the impact of non-synonymous DNA variations on protein function and human health. Predictive tools for protein stability are less accurate in predicting stabilizing variations compared to destabilizing ones, possibly due to the abundance of destabilizing variants in the available datasets. New methods should consider input features highly correlated with stabilizing variants and be tested on unbalanced datasets.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vladimir Sladek, Ryuhei Harada, Yasuteru Shigeta
Summary: The study demonstrates that the residue folding degree-based collective variable can track the evolution of secondary structures in protein dynamics, providing insight into the energy profiles and transition barriers during protein folding process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yoonbee Kim, Jong-Hoon Park, Young-Rae Cho
Summary: Network-based computational approaches are used for efficient disease-gene association prediction. This survey provides an overview of network-based disease-gene association prediction methods and shows that integrative methods perform better.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Castrense Savojardo, Giulia Babbi, Davide Baldazzi, Pier Luigi Martelli, Rita Casadio
Summary: This study investigates the association between MTHFR deficiency and protein structure variations. Using computational tools, the researchers explored the properties of 72 disease-associated missense variations in the MTHFR protein. They found that 61% of the variations destabilized the protein and corresponded to known deficiencies. The study also revealed unique patterns of disease-associated variations in the protein architecture of MTHFR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Rita Casadio, Pier Luigi Martelli, Castrense Savojardo
Summary: Proteins aggregates, known as biomolecular condensates, affect biological processes, and machine learning algorithms can be used to understand protein-protein interactions. More research is needed to improve our knowledge in this area.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Editorial Material
Biochemistry & Molecular Biology
Emanuela Leonardi, Castrense Savojardo, Giovanni Minervini
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Astronomy & Astrophysics
Egle Cekanaviciute, Duc Tran, Hung Nguyen, Alejandra Lopez Macha, Eloise Pariset, Sasha Langley, Giulia Babbi, Sherina Malkani, Sebastien Penninckx, Jonathan C. Schisler, Tin Nguyen, Gary H. Karpen, Sylvain. V. Costes
Summary: By studying 15 strains of mice, we identified single nucleotide polymorphisms associated with spontaneous and ionizing radiation-induced DNA damage. Statistical analysis revealed an association with pathways related to cellular signaling, metabolism, tumorigenesis, and nervous system damage. Our findings provide new mouse models for further studying the impact of ionizing radiation and validating genetic loci.
LIFE SCIENCES IN SPACE RESEARCH
(2023)
Article
Biochemical Research Methods
Athanasios Baltzis, Leila Mansouri, Suzanne Jin, Bjorn E. Langer, Ionas Erb, Cedric Notredame, Pier Luigi Martelli
Summary: This study found that protein sequence alignments estimated on AlphaFold2 predictions are nearly as accurate as those estimated on experimental structures, and they are significantly closer to the structural reference than sequence-based alignments. Furthermore, even low-quality AlphaFold2 structural models can be used to obtain highly accurate alignments. This suggests that AlphaFold2 encodes higher-order dependencies that can be utilized for sequence analysis.
Review
Biochemical Research Methods
Laura Marchetti, Riccardo Nifosi, Pier Luigi Martelli, Eleonora Da Pozzo, Valentina Cappello, Francesco Banterle, Maria Letizia Trincavelli, Claudia Martini, Massimo D'Elia
Summary: Recent biotechnological progress has enabled life scientists and physicians to access an unprecedented amount of data at all levels of biological complexity. Quantum computing approaches hold the promise to resolve, speed up, or refine the analysis of a wide range of computational problems.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
Castrense Savojardo, Davide Baldazzi, Giulia Babbi, Pier Luigi Martelli, Rita Casadio
Summary: Based on databases such as OMIM, Humsavar, Clinvar and Monarch, this study analyzes the association between human enzymes and genetic diseases, finding that 75% of them are rare diseases. By adopting the Mondo ontology initiative and Reactome pathways, a comprehensive understanding and categorization of the molecular mechanisms of diseases have been achieved.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Jacopo Martelossi, Giobbe Forni, Mariangela Iannello, Castrense Savojardo, Pier Luigi Martelli, Rita Casadio, Barbara Mantovani, Andrea Luchetti, Omar Rota-Stabelli
Summary: This study reports the draft genome of the subterranean termite Reticulitermes lucifugus, an economically important species with extensive research on its eusocial organization and mating system. The assembly covered a significant portion of the estimated genome size and showed complete homozygosity. The study identified numerous gene duplications associated with R. lucifugus diversification and significant lineage-specific expansions in gene families related to development, perception, and nutrient metabolism pathways. Additionally, a detailed analysis of P450 and odorant receptor gene repertoires revealed a wide diversity and dynamic evolutionary history. Overall, this newly assembled genome provides valuable insights into termite biology and pest control.
INSECT MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matteo Manfredi, Castrense Savojardo, Pier Luigi Martelli, Rita Casadio
Summary: This article introduces a method called ISPRED-SEQ for predicting protein-protein interaction sites based on protein sequences. It utilizes recently developed protein language models and deep neural networks, outperforming other similar methods.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elisa Bertolini, Giulia Babbi, Castrense Savojardo, Pier Luigi Martelli, Rita Casadio
Summary: MultiFacetedProtDB is a database of multifunctional human proteins, collecting comprehensive annotations and allowing searches for gene, protein, and associated structural and functional information. Studying multifunctional proteins helps elucidate the complexities of biological processes, particularly their importance and wide applications in human biology.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Giovanni Madeo, Castrense Savojardo, Matteo Manfredi, Pier Luigi Martelli, Rita Casadio
Summary: This article introduces a novel method called CoCoNat for predicting coiled-coil helix boundaries, residue-level register annotation, and oligomerization state. The method combines two state-of-the-art protein language models and implements a deep learning procedure with a Grammatical-Restrained Hidden Conditional Random Field. CoCoNat outperforms current state-of-the-art methods in residue-level and segment-level CCD, as well as in register annotation and prediction of oligomerization states.