Article
Multidisciplinary Sciences
Felix Wiggers, Samuel Wohl, Artem Dubovetskyi, Gabriel Rosenblum, Wenwei Zheng, Hagen Hofmann
Summary: Intrinsically disordered proteins form dynamic complexes with their ligands, with motions hidden in classical binding kinetics. By directly measuring dynamics in a highly mobile, high-affinity complex, researchers found that the energy landscape of the complex is rugged with small barriers reconciling specificity, high affinity, and extreme disorder. Single-molecule experiments and molecular simulations provide high resolution in space and time for resolving these motions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemical Research Methods
Xiaoli Zhao, Qianyi Wan, Jian Zhang, Yake Duan, Yong Li, Jingrong Ma, Chao Shi, Cuiping Ma
Summary: Here, we developed an ultra-fast and visual single-tube nucleic acid detection approach that combines the self-settling characteristics of chitosan-functionalized diatomaceous earth (CDE) and accelerated PCR (AC-PCR). This method not only improves the sensitivity and specificity of detection, but also allows for the completion of the entire process in a short period of time, with results visible to the naked eyes.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Andrew P. Latham, Bin Zhang
Summary: This study provides a critical review of existing coarse-grained force fields for disordered proteins and discusses the challenges in their application to folded proteins. It proposes an optimization strategy to improve the transferability of computer models across different protein types.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Fuhao Zhang, Bi Zhao, Wenbo Shi, Min Li, Lukasz Kurgan
Summary: This study presents the development of an innovative deep multi-task architecture, DeepDISOBind, which accurately predicts intrinsically disordered regions (IDRs) that interact with nucleic acids and proteins in protein sequences. The results show significant improvements in predictive accuracy compared to single-task designs and existing methods. Analysis of human proteome data demonstrates the ability of DeepDISOBind to accurately predict DNA- and RNA-binding proteins and protein hubs.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Biochemistry & Molecular Biology
Sushmita Basu, Daisuke Kihara, Lukasz Kurgan
Summary: One important characteristic of intrinsically disordered regions (IDRs) is their ability to interact with various molecules. In recent years, the prediction of binding IDRs in protein sequences has become more significant. These prediction tools utilize various predictive architectures, including scoring functions, regular expressions, traditional and deep machine learning, and meta-models. Efforts are currently focused on developing deep neural network-based architectures and expanding the coverage to include RNA, DNA, and lipid-binding IDRs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Engineering, Biomedical
Jon Arizti-Sanz, A'Doriann Bradley, Yibin B. Zhang, Chloe K. Boehm, Catherine A. Freije, Michelle E. Grunberg, Tinna-Solveig F. Kosoko-Thoroddsen, Nicole L. Welch, Priya P. Pillai, Sreekar Mantena, Gaeun Kim, Jessica N. Uwanibe, Oluwagboadurami G. John, Philomena E. Eromon, Gregory Kocher, Robin Gross, Justin S. Lee, Lisa E. Hensley, Bronwyn L. MacInnis, Jeremy Johnson, Michael Springer, Christian T. Happi, Pardis C. Sabeti, Cameron Myhrvold
Summary: SARS-CoV-2 and its variants can be visually detected via easy-to-use Cas13-based nucleic acid tests leveraging lyophilised reagents and fast sample inactivation at ambient temperature.
NATURE BIOMEDICAL ENGINEERING
(2022)
Review
Chemistry, Multidisciplinary
Agnieszka Tomaszewska-Antczak, Piotr Guga
Summary: This review summarizes the synthetic efforts on acyclic analogs of nucleic acids and evaluates their synthetic methods, thermal stability, and applications in biological and biochemical research as well as nanotechnology.
APPLIED SCIENCES-BASEL
(2021)
Article
Multidisciplinary Sciences
Anna Nemudraia, Artem Nemudryi, Murat Buyukyoruk, Andrew M. Scherffius, Trevor Zahl, Tanner Wiegand, Shishir Pandey, Joseph E. Nichols, Laina N. Hall, Aidan McVey, Helen H. Lee, Royce A. Wilkinson, Laura R. Snyder, Joshua D. Jones, Kristin S. Koutmou, Andrew Santiago-Frangos, Blake Wiedenheft
Summary: This study applies type-III CRISPR-based RNA capture and concentration technology to the detection of SARS-CoV-2, with advantages of rapidity, high sensitivity, and low cost.
NATURE COMMUNICATIONS
(2022)
Review
Biochemical Research Methods
Joakim Bohlin, Michael Matthies, Erik Poppleton, Jonah Procyk, Aatmik Mallya, Hao Yan, Petr Sulc
Summary: Molecular simulation is essential in DNA/RNA nanotechnology research, improving the precision of nanoscaffolds and diagnostic tools. oxView is a design tool for visualizing, designing, editing, and analyzing simulations of DNA, RNA, and nucleic acid-protein nanostructures, providing an accessible software platform for researchers to integrate simulation and 3D visualization into their projects.
Article
Biochemistry & Molecular Biology
Charles Christoffer, Daisuke Kihara
Summary: Proteins play key roles in cellular processes through physical interactions with other proteins and nucleic acids. Understanding the mechanisms of these processes requires considering the 3D structures of protein complexes. Protein docking has been used to computationally generate structure models, but flexibility consideration has been limited. New methods are needed to model ordered proteins undergoing large-scale conformational changes for elucidating their molecular-level functions.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ryohei Yamaji, Osamu Nakagawa, Yuki Kishimoto, Akane Fujii, Tomoki Matsumura, Taisuke Nakayama, Haruhiko Kamada, Takashi Osawa, Takao Yamaguchi, Satoshi Obika
Summary: This study demonstrates that using oligonucleotides (ONs) containing phenoxazine nucleobases can significantly enhance the therapeutic effect on mouse skeletal muscle diseases, which is of great importance for the treatment of skeletal muscle diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Anton Abyzov, Eckhard Mandelkow, Markus Zweckstetter, Nasrollah Rezaei-Ghaleh
Summary: The dynamics of a 441-residue long intrinsically disordered protein (IDP), tau protein, were investigated in the temperature range of 0-25 degrees C. The results suggest that at higher temperatures, the fast backbone conformational fluctuations and slower chain segmental motions of the protein might become inseparable. This study demonstrates the remarkable dynamic plasticity of this prototypical IDP and highlights the need for dynamic studies of IDPs at multiple temperatures.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemical Research Methods
Zhenling Peng, Zixia Li, Qiaozhen Meng, Bi Zhao, Lukasz Kurgan
Summary: One of the key features of IDRs is to facilitate interactions between proteins and nucleic acids. There are different types of disordered binding regions, including MoRFs, SLiMs, and longer binding domains. Recent research has introduced a new class of disordered binding regions called LIPs, which undergo disorderto-order transition upon binding. However, there are currently no dedicated sequence-based predictors for LIPs.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Zhenling Peng, Zixia Li, Qiaozhen Meng, Bi Zhao, Lukasz Kurgan
Summary: This paper introduces a new method for predicting intrinsically disordered regions (IDRs) called CLIP. CLIP uses inputs such as co-evolutionary information, physicochemical profiles, and disorder predictions to predict linear interacting peptides (LIPs) in protein sequences. Experimental results show that CLIP achieves good performance in predicting LIPs and outperforms current tools for predicting MoRFs and disordered protein-binding regions.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Brataraj Ghosh, Neelanjana Sengupta
Summary: This study reveals the impact of glucose as a molecular crowder on the solvent environment around protein surfaces in folded and intrinsically disordered states, showing differences in structural responses between the two states and the influence of glucose-induced crowding on hydration layers.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Emily J. Danoff, Karen G. Fleming
Article
Chemistry, Physical
Henry J. Lessen, Patrick J. Fleming, Karen G. Fleming, Alexander J. Sodt
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2018)
Editorial Material
Physiology
Karen G. Fleming
JOURNAL OF GENERAL PHYSIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Aaron P. Chum, Sophie R. Shoemaker, Patrick J. Fleming, Karen G. Fleming
Article
Chemistry, Multidisciplinary
Henry J. Lessen, Ananya Majumdar, Karen G. Fleming
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Chemistry, Multidisciplinary
Evan S. O'Brien, Brian Fuglestad, Henry J. Lessen, Matthew A. Stetz, Danny W. Lin, Bryan S. Marques, Kushol Gupta, Karen G. Fleming, A. Joshua Wand
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Biophysics
Rebecca F. Alford, Patrick J. Fleming, Karen G. Fleming, Jeffrey J. Gray
BIOPHYSICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Dagan C. Marx, Mathis J. Leblanc, Ashlee M. Plummer, Susan Krueger, Karen G. Fleming
Article
Multidisciplinary Sciences
Dagan C. Marx, Ashlee M. Plummer, Anneliese M. Faustino, Taylor Devlin, Michaela A. Roskopf, Mathis J. Leblanc, Henry J. Lessen, Barbara T. Amann, Patrick J. Fleming, Susan Krueger, Stephen D. Fried, Karen G. Fleming
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Chemistry, Multidisciplinary
Dagan C. Marx, Karen G. Fleming
Summary: This study determined an empirical correlation between the surface area of nonpolar side chains, transfer free energies, and local water concentration in the membrane, allowing for accurate estimation of Delta G(sc)(0) at any location in the bilayer. Additionally, the calculated interface-to-bilayer transfer free energy values were found to be similar to biological translocon-based transfer free energies, suggesting that the translocon mimics the bilayer interface energetically.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Anastassia A. Vorobieva, Paul White, Binyong Liang, Jim E. Horne, Asim K. Bera, Cameron M. Chow, Stacey Gerben, Sinduja Marx, Alex Kang, Alyssa Q. Stiving, Sophie R. Harvey, Dagan C. Marx, G. Nasir Khan, Karen G. Fleming, Vicki H. Wysocki, David J. Brockwell, Lukas K. Tamm, Sheena E. Radford, David Baker
Summary: Through computational design, researchers successfully developed novel TMBs with no homology to known TMBs, which can reversibly insert and fold into synthetic lipid membranes, and exhibit experimental structures highly similar to computational models. This advancement is expected to facilitate the custom design of pores for various applications.
Article
Biochemistry & Molecular Biology
Dagan C. Marx, Karen G. Fleming
Summary: Membrane protein folding studies have historically been challenging, but recent adaptations of methods have led to success in studying transmembrane proteins. Avoiding aggregation is crucial for the success of these experiments, and they have provided insights into folding trajectories, stabilizing forces, and more defined endpoints.Increased understanding of membrane protein folding in the cell has shown that emerging biophysical principles are largely recapitulated even in complex biological environments.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biophysics
Patrick J. J. Fleming, John J. J. Correia, Karen G. G. Fleming
Summary: Hydration of biological macromolecules is crucial for their stability and function. Traditional approaches to describe macromolecular hydration using a single parameter have limitations. This study presents a method to calculate two types of hydration: surface shell water and entrained water, which helps explain the hydration problem in hydrodynamics. The combination of these two types of hydration allows accurate calculation of hydrodynamic volume and various macromolecular properties.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2023)
Article
Multidisciplinary Sciences
Philip To, Yingzi Xia, Sea On Lee, Taylor Devlin, Karen G. Fleming, Stephen D. Fried
Summary: The process of protein folding is complex and important, involving cellular factors and processes. Researchers have developed a new method to monitor the structural changes of Escherichia coli proteins in the cell cytosol and with chaperones. The results show that GroEL can assist in refolding the majority of proteins, while DnaK and GroEL have a similar set of proteins that they refold. Additionally, some proteins are not able to be refolded with any chaperones.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)