Article
Biochemistry & Molecular Biology
Surekha Kanagarajan, Prabhu Dhamodharan, Nachiappan Mutharasappan, Sanjay Kumar Choubey, Prajisha Jayaprakash, Jayashree Biswal, Jeyakanthan Jeyaraman
Summary: The study focused on the structure and function of enzymes in the pyrimidine biosynthetic pathway, particularly the role of CAD enzymes in cellular mechanisms. Through molecular modeling and dynamics studies of CAD complexes, key residues impacting their binding mode and enzyme activity were identified.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Nicia Rosario-Ferreira, Alexandre M. J. J. Bonvin, Irina S. Moreira
Summary: Understanding protein-protein interactions is crucial in studying biomolecular assemblies. Hot-spot residues significantly impact the formation of protein-protein complexes. Recent research is focusing on AI techniques to replace traditional energy-based methodologies.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Article
Chemistry, Medicinal
Xin Xue, Ji-Bo Kang, Xiao Yang, Nan Li, Liang Chang, Juan Ji, Xiang-Kai Meng, Hai-Qing Zhang, Yue Zhong, Shao-Peng Yu, Wen-Yu Wu, Xiao-Long Wang, Nian-Guang Li, Shan-Liang Sun
Summary: The study identified key interaction points between HIF-1α and VHL, and successfully synthesized a series of new inhibitors for VHL/HIF-1α protein-protein interactions. These inhibitors showed improved binding affinity and stability in cellular assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pedro A. Rosario, Brian R. McNaughton
Summary: This study predicts hot-spot residues at the SARS-CoV-2 RBD/ACE2 binding interface using computational platforms, potentially guiding the development of reagents capable of disrupting this complex and halting COVID-19.
Article
Biochemistry & Molecular Biology
Krit Charupanit, Varomyalin Tipmanee, Thana Sutthibutpong, Praopim Limsakul
Summary: This study utilized computational methods to construct the protein sequence space of PETase-PET binding energy and identified mutation sites and appropriate side-chain properties that could enhance PETase activity. Molecular dynamics simulations revealed that PETase variants with S238C or Q119F may improve PETase efficiency. The findings have important implications for protein engineering and PETase improvement.
Article
Chemistry, Organic
Yi Wolf Zhang, Nan Zheng, Danny Hung-Chieh Chou
Summary: Phage display is a useful tool for discovering therapeutic antibodies and proteins. This study developed a new method for displaying insulin-like peptides on M13 phage, addressing the challenges posed by insulin's complex structure. The method has potential for displaying other structurally complex proteins on phage.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Chenchen Fu, Wenfeng Shen, Weina Li, Pan Wang, Luo Liu, Yangfang Dong, Jing He, Daidi Fan
Summary: In this study, a potential hyperthermophilic enzyme for ginsenosides biotransformation was discovered through molecular docking and mutagenesis. The mutated enzyme showed improved catalytic efficiency and substrate affinity compared to the wild-type enzyme, potentially due to a more stable conformational state. This study identified a promising candidate for industrial ginsenoside conversion.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2023)
Article
Mechanics
Roham Rafiee, Reza Shahzadi, Soheil Jafari
Summary: A multi-objective and multi-level optimization procedure is developed for obtaining optimal structural design of filament wound composite pipes in the oil and gas industries. The procedure integrates a hybrid design-optimization platform, combining a multi-objective genetic algorithm and a premutation-based direct search approach. It aims to minimize the cost of the pipe while maximizing other structural properties, taking into consideration manufacturing limitations and design requirements.
COMPOSITE STRUCTURES
(2022)
Article
Multidisciplinary Sciences
Hua Jiang, Fan Meng, Deren Lu, Yanjuan Chen, Guilin Luo, Yuejun Chen, Jun Chen, Cheng Chen, Xi Zhang, Dan Su
Summary: FastCloning is a widely used cloning technique in biomedical research labs. The HTFC method described here simplifies and improves the efficiency and reliability of parallel cloning.
Article
Microbiology
Nathaniel D. M. Holman, Anthony J. Wilkinson, Margaret C. M. Smith
Summary: In this study, the structure and function of S. coelicolor Pmt were investigated by mutating highly conserved residues. The results showed that substitutions of certain conserved residues led to loss of Pmt function, highlighting the importance of residue conservation for enzyme activity.
Article
Biochemistry & Molecular Biology
Andrew J. Lee, Masayuki Endo, Jamie K. Hobbs, A. Giles Davies, Christoph Walti
Summary: The study used DNA nanostructure-augmented high-speed AFM to directly observe the RecA-orchestrated alignment of homologous DNA strands, revealing transient sampling of micro-homology by RecA during the search for sequence alignment. These transient interactions are early steps in the search for sequence homology.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Xavier C. C. Giner, Kenley Joule Pierre, Nicholas M. M. Robert, Jacques J. J. Tremblay
Summary: The peptide hormone insulin-like 3 (INSL3) is mainly produced by Leydig cells and has various functions. The expression of the Insl3 gene in Leydig cells is regulated by multiple transcription factors, and a specific 35-bp region in the Insl3 promoter is responsible for its activity in Leydig cells. This region contains binding sites for several transcription factors and is crucial for Insl3 gene transcription.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Yuxi Lv, Song Luo, Kaifang Huang, Han Wang, Shuheng Dong, Yalong Cong, John Z. H. Zhang, Lili Duan
Summary: This study investigated the effect of bridging water on the binding of neuraminidase and two ligands, showing that the presence of bridging water enhances the stability and binding free energy of the complex. The study identified key residues in the neuraminidase-ligand complex and demonstrated that bridging water can regulate the hydrogen bond network to increase the number of hydrogen bonds, contributing to the stability of the complex and promoting binding.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Kyung-Hoon Lee, Krzysztof Kuczera
Summary: Prion diseases are caused by spongiform degeneration of the brain. This study investigates the destabilizing effects of three alanine mutations on the human prion protein. The results show that all three mutations decrease the stability of the protein, mainly due to van der Waals interactions. This research provides insights into the detailed mechanism of human prion protein destabilization and the role of specific residues.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Jack M. O' Shea, Angeliki Goutou, Jack Brydon, Cyrus R. Sethna, Christopher W. Wood, Sebastian Greiss
Summary: By using genetic code expansion to introduce photocaged amino acids and guided by computational modeling, we have developed a method to control the interaction between nanobodies and antigens. Upon photo-activation, nanobodies can restore their binding capability, allowing for precise control of protein function and localization in living organisms.
Article
Biochemistry & Molecular Biology
Joana Santos, Miguel Cardoso, Irina S. Moreira, Joao Goncalves, Joao D. G. Correia, Sandra Cabo Verde, Rita Melo
Summary: Biological therapies, such as recombinant proteins, are a promising approach towards precision medicine. Innovatively, the combination of in silico studies and experimental methods can optimize the production of recombinant proteins for targeted therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Carlos A. Barreto, Salete J. Baptista, Antonio J. Preto, Daniel Silverio, Rita Melo, Irina S. Moreira
Summary: This paper describes an exciting big data analysis compiled in a freely available database to characterize the coupling of different G-Protein coupled receptors (GPCRs) families with their intracellular partners. The opioid receptor (OR) family was used as a case study, with extensive characterization of all members and their corresponding binding partners. A multi-step approach including models' construction, complex assembling, and protein-protein interface characterization was performed, offering insights into GPCR coupling selectivity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemical Research Methods
Nicia Rosario-Ferreira, Victor Guimaraes, Vitor S. Costa, Irina S. Moreira
Summary: Blood cancers (BCs) cause over 720,000 deaths annually worldwide, making research in this area crucial. SicknessMiner is a valuable tool for extracting disease-disease relationships from raw input corpus, with results comparable to the DisGeNET resource.
BMC BIOINFORMATICS
(2021)
Review
Pharmacology & Pharmacy
Beatriz Bueschbell, Ana Beatriz Caniceiro, Pedro M. S. Suzano, Miguel Machuqueiro, Nicia Rosario-Ferreira, Irina S. Moreira
Summary: With over 10 million deaths per year, cancer is a transversal disease affecting both developed and developing regions. Multidrug resistance (MDR) remains the major hindrance to successful cancer therapy. Molecular profiling and artificial intelligence (AI) methods have the potential to enhance our understanding of cancer MDR. This review discusses common MDR mechanisms, compiles the most relevant omics public databases, and highlights AI methods contributing to advances in cancer research.
DRUG RESISTANCE UPDATES
(2022)
Article
Chemistry, Multidisciplinary
Nicia Rosario-Ferreira, Alexandre M. J. J. Bonvin, Irina S. Moreira
Summary: Understanding protein-protein interactions is crucial in studying biomolecular assemblies. Hot-spot residues significantly impact the formation of protein-protein complexes. Recent research is focusing on AI techniques to replace traditional energy-based methodologies.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Article
Biochemical Research Methods
Nicia Rosario-Ferreira, Salete J. Baptista, Carlos A. Barreto, Filipe E. P. Rodrigues, Tomas F. D. Silva, Sara G. F. Ferreira, Joao N. M. Vitorino, Rita Melo, Bruno L. Victor, Miguel Machuqueiro, Irina S. Moreira
Summary: This study introduced computational protocols for targeting the SARS-CoV-2 main protease, including uploading, visualizing, and managing three-dimensional structures, homology modeling, protein-ligand docking, virtual screening, and molecular dynamics simulations. These protocols offer important insights into addressing one of the biggest biological problems currently facing the world.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Neurosciences
Ana B. B. Caniceiro, Beatriz Bueschbell, Anke C. C. Schiedel, Irina S. S. Moreira
Summary: Neurodegenerative diseases affect over 30 million people worldwide with an ascending trend. The pathophysiology of these diseases is partially known, but the point at which a disease turns degenerative remains unclear. Current therapeutics for these diseases have limitations in long-term treatment. G protein-coupled receptors (GPCRs) have been shown to play a significant role in neurodegenerative diseases, offering promise in understanding their biological mechanism.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
G. L. Caldeira, A. S. Inacio, N. Beltrao, C. A. Barreto, M. Rodrigues, T. Rondao, R. Macedo, R. P. Gouveia, M. Edfawy, J. Guedes, B. Cruz, S. R. Louros, I. S. Moreira, J. Peca, A. L. Carvalho
Summary: This study identifies a mutated form of the stargazin protein that is associated with intellectual disability. The findings reveal a causal role for mutated stargazin in the pathogenesis of intellectual disability and uncover a new role for stargazin in the development and function of hippocampal synapses.
MOLECULAR PSYCHIATRY
(2022)
Article
Engineering, Biomedical
Tiffany S. Pinho, Deolinda Silva, Jorge Cibrao Ribeiro, Ana Marote, Rui Lima, Salete J. Batista, Rita Melo, Clarisse Ribeiro, Cristiana B. Cunha, Irina S. Moreira, Senentxu Lanceros-Mendez, Antonio J. Salgado
Summary: This study focuses on the application of poled and coated PVDF films for neural differentiation and found that these films can induce neuronal differentiation under mechanical stimulation, which is further enhanced with a pre-coating step of poly-d-lysine and laminin.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2023)
Article
Chemistry, Multidisciplinary
A. J. Preto, Paulo C. Correia, Irina S. Moreira
Summary: DrugTax is an easy-to-use Python package for detailed characterization and chemical taxonomy of small molecules, suitable for AI approaches and drug discovery pipelines. It offers a range of features and tools for analysis and visualization.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Ana B. Caniceiro, Beatriz Bueschbell, Carlos A. V. Barreto, Antonio J. Preto, Irina S. Moreira
Summary: G protein-coupled receptors (GPCRs) play important roles in regulating multiple signaling pathways. Mutations in GPCR genes can significantly impact receptor structure and function. This study constructed a computational framework called MUG (Mutations Understanding GPCRs) to explore known mutations and their effects on the A17 subfamily of GPCRs. The results revealed a diverse range of mutations in A17 subfamily structures, particularly in conserved residues and domains. The mutated residues were often located at ligand binding pockets and activating microdomains, potentially disrupting receptor function. The interactive web application MUG was developed to facilitate the management and visualization of this dataset.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemical Research Methods
Luiz Felipe Piochi, Antonio J. Preto, Irina S. Moreira
Summary: To tackle the challenge of cancer treatment, a new drug response prediction algorithm called Drug Efficacy Leveraging Forked and Specialized networks (DELFOS) was developed. It utilizes multi-omics data from 65 cancer cell lines and structural data from over 200 compounds to predict drug sensitivity. Incorporating single-cell expression data to predict drug response was also evaluated. DELFOS was validated using datasets with unseen cell lines or drugs and compared with other state-of-the-art algorithms, achieving high prediction performance on several correlation and error metrics. Overall, DELFOS effectively leverages multi-omics data for the prediction of drug responses in thousands of drug-cell line pairs.
Article
Biology
Antonio J. Preto, Pedro Matos-Filipe, Joana Mourao, Irina S. Moreira
Summary: This study introduces SYNPRED, an interdisciplinary approach that uses AI algorithms to predict anticancer drug synergy. By using 5 reference models and AI algorithms, SYNPRED achieves the best predictive performance and identifies the most suitable reference model for synergy prediction. Additionally, SYNPRED focuses on data interpretability and creates a simple web-based application for easy access by nonexpert researchers.
Article
Biochemistry & Molecular Biology
Catarina Marques-Pereira, Manuel N. Pires, Raquel P. Gouveia, Nadia N. Pereira, Ana B. Caniceiro, Nicia Rosario-Ferreira, Irina S. Moreira
Summary: This study examined the structural characteristics of the Membrane (M) protein of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and predicted its dimeric structure and membrane orientation using computational methods. The study also identified a number of mutation sites in the M protein that appeared in variants of the virus, which could have implications for the development of new therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Mathematical & Computational Biology
Pedro Matos-Filipe, Antonio J. Preto, Panagiotis Koukos, Joana Mourao, Alexandre M. J. J. Bonvin, Irina S. Moreira
Summary: Membrane proteins play crucial roles in cellular processes and are targeted by a significant percentage of FDA-approved drugs. However, the lack of structural and mechanistic information due to their location within the lipid bilayer is a major challenge. MENSAdb is an interactive web application developed to enhance the understanding of dimeric MPs by summarizing their evolutionary and physicochemical properties, providing valuable insights into their formation principles.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2021)