Article
Biochemistry & Molecular Biology
Chang Liu, Zhizhen Li, Zonghan Liu, Shiye Yang, Qing Wang, Zongtao Chai
Summary: This study revealed the conformational dynamics of the phosphate-binding loop (P-loop) in different states of STK17B through molecular dynamics simulation. The interactions between the P-loop and inhibitors were found to contribute to inhibitor selectivity profile. These findings advance our understanding of kinase inhibitor selectivity and have implications for the design of selective inhibitors for other protein kinases.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Hector Vazquez
Summary: This method uses density functional theory to calculate the tunneling conductance of single molecule junctions, simplifying the model and reducing computational costs significantly, while also quantifying the relationship between molecular structure and conductance.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Physical
Hector Vazquez
Summary: A method is proposed to calculate the tunneling conductance of single molecule junctions using density functional theory. The method reduces computational cost significantly and allows for large-scale conductance calculations, providing a possibility to study the relationship between molecular structure and conductance.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Tanmoy Khan, Nilimesh Das, Kuldeep Singh Negi, Suman Bhowmik, Pratik Sen
Summary: This study investigates the solvation dynamics, conformational fluctuation dynamics, and stability of proteins in deep eutectic solvents (DESs). The results show that the side-chain flexibility and thermal stability of proteins decrease gradually with increasing DES concentration. However, the associated water dynamics only marginally slow down at higher DES concentrations.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Multidisciplinary Sciences
Federico Riva, Caio Graco-Roza, Gergana N. Daskalova, Emma J. Hudgins, Jayme M. M. Lewthwaite, Erica A. Newman, Masahiro Ryo, Stefano Mammola
Summary: Ecological systems are complex and understanding complexity is crucial for progress in ecology and conservation. However, multiple definitions of complexity and excessive reliance on traditional scientific approaches hinder conceptual advances. By analyzing articles referring to ecological complexity, we find that the study of complexity in ecology is diverse and weakly related to complex system science. Current research trends focus on basic theory, scaling, and macroecology. We propose a more coherent and cohesive approach to studying complexity in ecology based on our review and generalities identified.
Article
Biochemistry & Molecular Biology
Valentina J. Liebich, Olga Avrutina, Jan Habermann, Laura M. Hillscher, Markus Langhans, Tobias Meckel, Markus Biesalski, Harald Kolmar
Summary: A novel two-step method for covalent, site-directed, and efficient immobilization of proteins on lab-made paper sheets was reported. Four different conjugation strategies for peptide immobilization were evaluated for reproducibility and fiber loading efficiency, with the two enzymes tested showing suitable controlled oriented linkage of substrate proteins at physiological conditions.
Article
Biochemical Research Methods
Sara Ibrahim Omar, Meng Zhao, Rohith Vedhthaanth Sekar, Sahar Arbabi Moghadam, Jack A. Tuszynski, Michael T. Woodside
Summary: The coronavirus responsible for COVID-19 controls viral protein production through a unique RNA pseudoknot structure, which may be a potential target for treating the disease. Computational modeling revealed multiple possible conformations of the SARS-CoV-2 pseudoknot, providing insight for future experiments and drug discovery efforts. The study also identified unusual structures involving RNA threading through helical junctions, which could aid in understanding and developing treatments for SARS-CoV-2.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Review
Multidisciplinary Sciences
Marta Bordonhos, Tiago L. P. Galvao, Jose R. B. Gomes, Jose D. Gouveia, Miguel Jorge, Mirtha A. O. Lourenco, Jose M. Pereira, German Perez-Sanchez, Moises L. Pinto, Carlos M. Silva, Joao Tedim, Bruno Zezere
Summary: This article presents an overview of a collaborative research effort on computational approaches to understand materials and tools at different length and time scales. It introduces various techniques and models used in the study, as well as recent computational case studies focusing on material synthesis, interpretation of experimental results, prediction of material properties, and material selection for specific applications.
ADVANCED THEORY AND SIMULATIONS
(2023)
Article
Biochemistry & Molecular Biology
Silvia Rinaldi, Giorgio Colombo, Antonella Paladino
Summary: In this study, we investigate the mechanism behind t1-dependent regulation and the impact of different t1 nucleotides on the conformational dynamics of hAgo2 and guide-target RNAs. Our findings demonstrate that t1-adenine plays a crucial role in the recognition and stabilization of the target, acting as a molecular switch. The results provide important insights into the regulation of gene expression.
Article
Biochemistry & Molecular Biology
Milosz Ruszkowski, Giuseppe Forlani
Summary: This study determined the structure of EPSPS from the plant model species Arabidopsis thaliana and explored its susceptibility to glyphosate inhibition. The crystal structure of the enzyme was resolved, providing insights for the design of novel EPSPS inhibitors.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Physics, Applied
Jamoliddin Razzokov, Sunnatullo Fazliev, Dinora Erkinova, Shavkat Mamatkulov, Zhitong Chen
Summary: This study investigated the effects of reactive oxygen and nitrogen species (RONS) on the human epidermal growth factor (hEGF) through molecular dynamics simulations. The results showed that nitrosylation induced conformational changes in hEGF and disruption of disulfide bonds, but the structural stability of hEGF remained mostly unaffected.
JOURNAL OF PHYSICS D-APPLIED PHYSICS
(2022)
Review
Green & Sustainable Science & Technology
Pablo Manzano, Daniel Burgas, Luis Cadahia, Jussi T. Eronen, Alvaro Fernandez-Llamazares, Slimane Bencherif, Oystein Holand, Oula Seitsonen, Bayarmaa Byambaa, Mikael Fortelius, Maria E. Fernandez-Gimenez, Kathleen A. Galvin, Mar Cabeza, Nils Chr Stenseth
Summary: The article proposes a transdisciplinary research approach to understand pastoralist transitions using social, economic, and environmental dimensions, diverse geographic contexts and scales, and timescales from the distant past to the present. Developing indicators within a social-ecological resilience analytical framework helps improve understanding of system transitions and supports better-informed decision making. The need for a paradigm shift in pastoralism science and policy is urgent, and the research approach, including participatory methods, can provide the necessary solutions.
Article
Materials Science, Multidisciplinary
Alfonso Pedone, Valeria Cannillo, Maria Cristina Menziani
Summary: This study used Molecular Dynamics simulations to obtain reliable structural models of different glasses and interpret their behavior and properties. The substitution of sodium oxide with alkaline earth oxides in the traditional 45S5 Bioglass was shown to improve sinterability and mechanical properties while maintaining biocompatibility. The study provides insights on structure-properties relationships in bioactive glasses, offering guidelines for designing innovative compositions with desired properties for specific applications.
Article
Multidisciplinary Sciences
Tae Hun Kim, Michael L. Nosella, Nicolas Bolik- Coulon, Robert W. Harkness, Shuya Kate Huang, Lewis E. Kay
Summary: Epigenetic modifications of chromatin, including acetylation of histone lysine residues, are crucial for regulating genetic information and protein synthesis. This study investigates the effects of histone acetylation on the structural dynamics of nucleosomes and their interactions with protein factors. The findings reveal nuanced changes to nucleosome dynamics and highlight the importance of different acetylation patterns in controlling biological output.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Physical
Alena Klindziuk, Anatoly B. Kolomeisky
Summary: Transcription, a fundamental biological process, has been found to exhibit dynamic behavior of alternating between productive and inactive phases, known as transcriptional bursting. Despite significant attention from researchers, the microscopic origin and biological functions of transcriptional bursting remain unclear.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Nivedita Rajendiran, Jacob D. Durrant
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2018)
Article
Biochemical Research Methods
Jacob D. Durrant
Article
Chemistry, Multidisciplinary
Patrick J. Ropp, Jacob O. Spiegel, Jennifer L. Walker, Harrison Green, Guillermo A. Morales, Katherine A. Milliken, John J. Ringe, Jacob D. Durrant
JOURNAL OF CHEMINFORMATICS
(2019)
Article
Chemistry, Medicinal
Sayuri Pacheco, Jesse C. Karninsky, Iurii K. Kochnev, Jacob D. Durrant
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Biochemistry & Molecular Biology
Kevin C. Cassidy, Roni M. Lahr, Jesse C. Kaminsky, Stephanie Mack, Bruno D. Fonseca, Subha R. Das, Andrea J. Berman, Jacob D. Durrant
Article
Chemistry, Multidisciplinary
Jacob D. Durrant, Sarah E. Kochanek, Lorenzo Casalino, Pek U. Ieong, Abigail C. Dommer, Rommie E. Amaro
ACS CENTRAL SCIENCE
(2020)
Article
Biochemical Research Methods
Yuri Kochnev, Erich Hellemann, Kevin C. Cassidy, Jacob D. Durrant
Review
Genetics & Heredity
Jacob O. Spiegel, Bennett Van Houten, Jacob D. Durrant
Summary: PARP1 is a multifunctional enzyme involved in DNA repair pathways. Pharmacological inhibition of PARP1 is used to treat certain cancers, but resistance is common, highlighting the need for novel therapeutic approaches.
Article
Chemistry, Medicinal
Harrison Green, Jacob D. Durrant
Summary: Lead optimization in drug discovery involves modifying small-molecule ligands to improve properties like binding affinity. DeepFrag, a deep-learning model for this purpose, has been made more accessible through the creation of a user-friendly browser app that eliminates the need for uploading structures or installing additional software.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Jade Young, Neerja Garikipati, Jacob D. Durrant
Summary: BINANA is an algorithm used to identify and characterize receptor/ligand interactions. The algorithm has been updated to be more accessible and can now be used for analysis in web browsers. A web-browser application has been created to allow students and chemical-biology researchers to visualize receptor/ligand complexes and their binding interactions quickly.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemical Research Methods
Erich Hellemann, Jennifer L. Walker, Mitchell A. Lesko, Dakshayini G. Chandrashekarappa, Martin C. Schmidt, Allyson F. O'Donnell, Jacob D. Durrant
Summary: Glucose plays a central role in various biological processes, acting as an energy source and a building block for biosynthesis. A new spontaneous mutation in hexokinase-2, hxk2(G238v), has been discovered that confers resistance to a toxic glucose analog. Molecular dynamics simulations reveal how this mutation affects the protein structure and catalytic function. This study provides new insights into the structure of glucose metabolism regulator and its implications in cancer biology and drug resistance.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ann Wang, Jacob D. Durrant
Summary: This article outlines the importance of open-source, accessible tools for computer-aided drug discovery (CADD) and proposes a browser-based approach to CADD tool deployment. The advantages and need for browser apps are highlighted.
Article
Chemistry, Physical
Erich Hellemann, Jacob D. Durrant
Summary: Structure-based virtual screening is effective for identifying potential small-molecule ligands. However, traditional approaches struggle to find ligands that bind to alternate conformations. Ensemble docking addresses this issue but requires methods to thoroughly explore pocket flexibility. We introduce Sub-Pocket EXplorer (SubPEx), which uses weighted ensemble path sampling to accelerate binding-pocket sampling.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Harrison Green, David R. Koes, Jacob D. Durrant
Summary: Machine learning has been increasingly applied in the field of computer-aided drug discovery, showing notable advances in binding-affinity prediction, virtual screening, and QSAR. A deep convolutional neural network was used to predict appropriate fragments based on the structure of a receptor/ligand complex, with an efficiency of about 58% in selecting correct fragments from known ligands. The trained DeepFrag model and its associated software have been released under the Apache License, Version 2.0.
Article
Chemistry, Multidisciplinary
Emily J. Ha, Cara T. Lwin, Jacob D. Durrant
JOURNAL OF CHEMINFORMATICS
(2020)