TIES 2.0: A Dual-Topology Open Source Relative Binding Free Energy Builder with Web Portal.
Ontology highlight
ABSTRACT:
SUBMITTER: Bieniek MK
PROVIDER: S-EPMC9930115 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Publications
TIES 2.0: A Dual-Topology Open Source Relative Binding Free Energy Builder with Web Portal.
Bieniek Mateusz K MK Wade Alexander D AD Bhati Agastya P AP Wan Shunzhou S Coveney Peter V PV
Journal of chemical information and modeling 20230131 3
Relative binding free energy (RBFE) calculations are widely used to aid the process of drug discovery. TIES, Thermodynamic Integration with Enhanced Sampling, is a dual-topology approach to RBFE calculations with support for NAMD and OpenMM molecular dynamics engines. The software has been thoroughly validated on publicly available datasets. Here we describe the open source software along with a web portal (https://ccs-ties.org) that enables users to perform such calculations correctly and rapid ...[more]
Similar Datasets
Project description:Automated free energy calculations for the prediction of binding free energies of congeneric series of ligands to a protein target are growing in popularity, but building reliable initial binding poses for the ligands is challenging. Here, we introduce the open-source FEgrow workflow for building user-defined congeneric series of ligands in protein binding pockets for input to free energy calculations. For a given ligand core and receptor structure, FEgrow enumerates and optimises the bioactive conformations of the grown functional group(s), making use of hybrid machine learning/molecular mechanics potential energy functions where possible. Low energy structures are optionally scored using the gnina convolutional neural network scoring function, and output for more rigorous protein-ligand binding free energy predictions. We illustrate use of the workflow by building and scoring binding poses for ten congeneric series of ligands bound to targets from a standard, high quality dataset of protein-ligand complexes. Furthermore, we build a set of 13 inhibitors of the SARS-CoV-2 main protease from the literature, and use free energy calculations to retrospectively compute their relative binding free energies. FEgrow is freely available at https://github.com/cole-group/FEgrow, along with a tutorial.
| S-EPMC9607723 | biostudies-literature
Project description:In this work we present significant improvements to the open-source all-iron battery. We show higher power density and simpler fabrication. We also show a more reproducible procedure for preparing the electrolytes. The results are a highly rechargeable electrochemical cell based on iron, chloride, sulfate, and potassium ions in water at near-neutral pH. The cell is stable for thousands of cycles. It displays modest energy density consistent with the previous all-iron battery. The current is improved by a factor of 10 to a practical level of 500 mA/L and is able to deliver a maximal power of 250 mW/L. While this is modest performance compared to commercial rechargeable batteries, its low cost, simple synthesis, and safe manufacturing may make it suitable for storing renewable energy.
| S-EPMC9041250 | biostudies-literature
Project description:Single-cell RNA-seq (scRNA-seq) is a powerful genomics technology to interrogate the cellular composition and behaviors of complex systems. While the number of scRNA-seq datasets and available computational analysis tools have grown exponentially, there are limited systematic data sharing strategies to allow rapid exploration and re-analysis of single-cell datasets, particularly in the cardiovascular field. We previously introduced PlaqView, an open-source web portal for the exploration and analysis of published atherosclerosis single-cell datasets. Now, we introduce PlaqView 2.0 (www.plaqview.com), which provides expanded features and functionalities as well as additional cardiovascular single-cell datasets. We showcase improved PlaqView functionality, backend data processing, user-interface, and capacity. PlaqView brings new or improved tools to explore scRNA-seq data, including gene query, metadata browser, cell identity prediction, ad hoc RNA-trajectory analysis, and drug-gene interaction prediction. PlaqView serves as one of the largest central repositories for cardiovascular single-cell datasets, which now includes data from human aortic aneurysm, gene-specific mouse knockouts, and healthy references. PlaqView 2.0 brings advanced tools and high-performance computing directly to users without the need for any programming knowledge. Lastly, we outline steps to generalize and repurpose PlaqView's framework for single-cell datasets from other fields.
| S-EPMC9393487 | biostudies-literature
Project description:In the genomic era, data dissemination and visualization is an integral part of scientific publications and research projects involving international consortia producing massive genome-wide data sets, intra-organizational collaborations, or individual labs. However, creating custom supporting websites is oftentimes impractical due to the required programming effort, web server infrastructure, and data storage facilities, as well as the long-term maintenance burden. ZENBU-Reports (https://fantom.gsc.riken.jp/zenbu/reports) is a web application to create interactive scientific web portals by using graphical interfaces while providing storage and secured collaborative sharing for data uploaded by users. ZENBU-Reports provides the scientific visualization elements commonly used in supplementary websites, publications and presentations, presenting a complete solution for the interactive display and dissemination of data and analysis results during the full lifespan of a scientific project both during the active research phase and after publication of the results.
| S-EPMC10440783 | biostudies-literature
Project description:ObjectivesThe research evaluated participant satisfaction with the content and format of the "Web 2.0 101: Introduction to Second Generation Web Tools" course and measured the impact of the course on participants' self-evaluated knowledge of Web 2.0 tools.MethodsThe "Web 2.0 101" online course was based loosely on the Learning 2.0 model. Content was provided through a course blog and covered a wide range of Web 2.0 tools. All Medical Library Association members were invited to participate. Participants were asked to complete a post-course survey. Respondents who completed the entire course or who completed part of the course self-evaluated their knowledge of nine social software tools and concepts prior to and after the course using a Likert scale. Additional qualitative information about course strengths and weaknesses was also gathered.ResultsRespondents' self-ratings showed a significant change in perceived knowledge for each tool, using a matched pair Wilcoxon signed rank analysis (P<0.0001 for each tool/concept). Overall satisfaction with the course appeared high. Hands-on exercises were the most frequently identified strength of the course; the length and time-consuming nature of the course were considered weaknesses by some.ConclusionLearning 2.0-style courses, though demanding time and self-motivation from participants, can increase knowledge of Web 2.0 tools.
| S-EPMC2759158 | biostudies-literature
Project description:In a routine clinical environment or clinical trial, a case report form or structured reporting template can be used to quickly generate uniform and consistent reports. Annotation and image markup (AIM), a project supported by the National Cancer Institute's cancer biomedical informatics grid, can be used to collect information for a case report form or structured reporting template. AIM is designed to store, in a single information source, (a) the description of pixel data with use of markups or graphical drawings placed on the image, (b) calculation results (which may or may not be directly related to the markups), and (c) supplemental information. To facilitate the creation of AIM annotations with data entry templates, an AIM template schema and an open-source template creation application were developed to assist clinicians, image researchers, and designers of clinical trials to quickly create a set of data collection items, thereby ultimately making image information more readily accessible.
| S-EPMC3393884 | biostudies-other
Project description:Free-energy calculations play an important role in the application of computational chemistry to a range of fields, including protein biochemistry, rational drug design, or materials science. Importantly, the free-energy difference is directly related to experimentally measurable quantities such as partition and adsorption coefficients, water activity, and binding affinities. Among several techniques aimed at predicting free-energy differences, perturbation approaches, involving the alchemical transformation of one molecule into another through intermediate states, stand out as rigorous methods based on statistical mechanics. However, despite the importance of free-energy calculations, the applicability of the perturbation approaches is still largely impeded by a number of challenges, including the definition of the perturbation path, i.e., alchemical changes leading to the transformation of one molecule to the other. To address this, an automatic perturbation topology builder based on a graph-matching algorithm is developed, which can identify the maximum common substructure (MCS) of two or multiple molecules and provide the perturbation topologies suitable for free-energy calculations using the GROMOS and the GROMACS simulation packages. Various MCS search options are presented leading to alternative definitions of the perturbation pathway. Moreover, perturbation topologies generated using the default multistate MCS search are used to calculate the changes in free energy between lysine and its two post-translational modifications, 3-methyllysine and acetyllysine. The pairwise free-energy calculations performed on this test system led to a cycle closure of 0.5 ± 0.3 and 0.2 ± 0.2 kJ mol-1, with GROMOS and GROMACS simulation packages, respectively. The same relative free energies between the three states are obtained by employing the enveloping distribution sampling (EDS) approach when compared to the pairwise perturbations. Importantly, this toolkit is made available online as an open-source Python package (https://github.com/drazen-petrov/SMArt).
| S-EPMC8479811 | biostudies-literature
Project description:Proteins mediate and perform various fundamental functions of life. This versatility of protein function is an attribute of its 3D structure. In recent years, our understanding of protein 3D structure has been complemented with advances in computational and mathematical tools for protein modelling and protein design. 3D molecular visualisation is an essential part in every protein design and protein modelling workflow. Over the years, stand-alone and web-based molecular visualisation tools have been used to emulate three-dimensional view on computers. The advent of virtual reality provided the scope for immersive control of molecular visualisation. While these technologies have significantly improved our insights into protein modelling, designing new proteins with a defined function remains a complicated process. Current tools to design proteins lack user-interactivity and demand high computational skills. In this work, we present the Pepblock Builder VR, a gaming-based molecular visualisation tool for bio-edutainment and understanding protein design. Simulating the concepts of protein design and incorporating gaming principles into molecular visualisation promotes effective game-based learning. Unlike traditional sequence-based protein design and fragment-based stitching, the Pepblock Builder VR provides a building block style environment for complex structure building. This provides users a unique visual structure building experience. Furthermore, the inclusion of virtual reality to the Pepblock Builder VR brings immersive learning and provides users with "being there" experience in protein visualisation. The Pepblock Builder VR works both as a stand-alone and VR-based application, and with a gamified user interface, the Pepblock Builder VR aims to expand the horizons of scientific data generation to the masses.
| S-EPMC8160467 | biostudies-literature
Project description:The number of online data repositories is growing and they are becoming increasingly difficult to navigate. Data are scattered among different repositories, or hidden on personal or institutional servers. To access data, users must search extensively and rely on site-specific tools. These hurdles substantially inhibit data findability and accessibility; in particular, those in the long tail of data. We developed an open source web application, Spatial Data Hub, that is a geospatial data index, connected to remote Internet sources. It allows simultaneous display and comparison of disparate datasets on a single map. It aims to promote all data equally and provide the flexibility to connect to any storage system, effectively making long-tail datasets as visible as those in large, established repositories. Its low barrier of entry allows scientists and organizations to easily add data throughout the research process; enhancing transparency, openness and reproducibility. This flexibility and functionality makes Spatial Data Hub a novel platform for researchers to promote their work, develop new hypotheses and create new collaborations.
| S-EPMC6371891 | biostudies-other
Project description:Cytoskeletal pattern formation and structural dynamics are key to a variety of biological functions and a detailed and quantitative analysis yields insight into finely tuned and well-balanced homeostasis and potential pathological alterations. High content life cell imaging of fluorescently labeled cytoskeletal elements under physiological conditions is nowadays state-of-the-art and can record time lapse data for detailed experimental studies. However, systematic quantification of structures and in particular the dynamics (i.e. frame-to-frame tracking) are essential. Here, an unbiased, quantitative, and robust analysis workflow that can be highly automatized is needed. For this purpose we upgraded and expanded our fiber detection algorithm FilamentSensor (FS) to the FilamentSensor 2.0 (FS2.0) toolbox, allowing for automatic detection and segmentation of fibrous structures and the extraction of relevant data (center of mass, length, width, orientation, curvature) in real-time as well as tracking of these objects over time and cell event monitoring.
| S-EPMC9901806 | biostudies-literature