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Motivation: In experimental protein engineering, alanine-scanning mutagenesis involves the replacement of selected residues with alanine to determine the energetic contribution of each side chain to forming an interaction. For example, it is often used to study protein-protein interactions. However, such experiments can be time-consuming and costly, which has led to the development of programmes for performing computational alanine-scanning mutagenesis (CASM) to guide experiments. While programmes are available for this, there is a need for a real-time web application that is accessible to non-expert users.
Results: Here, we present BAlaS, an interactive web application for performing CASM via BudeAlaScan and visualizing its results. BAlaS is interactive and intuitive to use. Results are displayed directly in the browser for the structure being interrogated enabling their rapid inspection. BAlaS has broad applications in areas, such as drug discovery and protein-interface design.
Availability And Implementation: BAlaS works on all modern browsers and is available through the following website: https://balas.app. The project is open source, distributed using an MIT license and is available on GitHub (https://github.com/wells-wood-research/balas).
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http://dx.doi.org/10.1093/bioinformatics/btaa026 | DOI Listing |
iScience
August 2025
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Understanding the breadth and functional profile of T cell responses is crucial for assessing their role in immune surveillance of emerging SARS-CoV-2 variants. Sampling healthy individuals, we profiled the kinetics and polyfunctionality of T cell immunity elicited by mRNA vaccination. Modeling of anti-spike T cell responses against ancestral and variant strains suggested epitope immunodominance and cross-reactivity as major predictive determinants of T cell immunity.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran.
L-asparaginase, a key biocatalyst for therapeutic and industrial applications, is often limited by poor thermal stability. A novel L-asparaginase gene from Bacillus sp. SD3 was identified, cloned, expressed, and characterized.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
NYU-ECNU Center for Computational Chemistry and Shanghai Frontiers Science Center of Artificial Intelligence and Deep Learning, NYU Shanghai, Shanghai 200124, China; Department of Chemistry, New York University, New York, New York 10003, USA; Binary Biotechnology LTD, Shenzhen, China; Faculty of Syn
Interleukin-37b (IL-37b) has emerged as a potential therapeutic agent for inflammatory diseases. However, IL-37b tends to self-assemble into a dimeric form, which compromises its anti-inflammatory efficacy. Furthermore, the currently active monomeric variants of IL-37b are unstable, limiting their clinical utility.
View Article and Find Full Text PDFMolecules
July 2025
School of Mathematics, Physics and Statistics, Shanghai University of Engineering Science, Shanghai 201620, China.
The design of small-molecule inhibitors targeting proprotein convertase subtilisin/Kein type 9 (PCSK9) remains a forefront challenge in combating atherosclerosis. While various monoclonal antibodies have achieved clinical success, small-molecule inhibitors are hindered by the unique structural features of the PCSK9 binding interface. In this study, a potential small-molecule inhibitor was identified through virtual screening, followed by molecular dynamics (MD) simulations to explore the binding mechanisms between the inhibitor and the PCSK9 protein.
View Article and Find Full Text PDFProtein Sci
July 2025
Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Escherichia coli RfaH, a member of the universally conserved NusG family of transcription factors, regulates its function by undergoing a structural rearrangement of its C-terminal domain (CTD) upon recruitment to RNA polymerase (RNAP) paused at the DNA signal known as operon polarity suppressor (ops) element. While it is known that the fold-switch of RfaH CTD from an α-helical hairpin (autoinhibited state) into a β-barrel (active state) is controlled by interactions between the N-terminal domain (NTD) and CTD, which are broken apart upon NTD binding to RNAP, a comprehensive analysis of residues that stabilize the autoinhibited state is lacking. Here, we utilize a combination of molecular dynamics (MD), protein structure prediction, and in vivo functional assays as a workflow to determine key interdomain (ID) residues controlling the fold-switch of RfaH.
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