14 papers · ranked by Valyu relevance
Authors not listed
Protein conformational landscapes contain the functionally relevant information useful for understanding biological processes. Mapping out conformational landscapes provides valuable insights into protein behaviors and biological phenomena, and has relevance to therapeutic design. While experimental structural biology…
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Computing electrostatic interactions remains the bottleneck of molecular dynamics (MD) simulations despite more than a century of effort in developing methods to accelerate the calculation. Previously we have developed the Spherical Grid and Treecode (SGT) and Gauss-Legendre-Spherical-t (GLST) algorithms for…
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With the ever-increasing demand for atomistic structures representative of real-life systems as well as the ad-vent of exascale computers, it has now become necessary and possible to use advanced global optimization (GO) techniques to intelligently sample the potential energy surface (PES). Given the previous studies…
Bo Li, Joshua Parker, Joel Tong, Thomas Kodadek
Macrocyclic peptides (MPs) are a class of compounds that have been shown to be particu-larly well suited for engaging difficult protein targets. However, their utility is limited by their generally poor cell permeability and bioavailability. Here we report an efficient solid-phase synthesis of novel MPs by trapping a…
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Cyclic peptides become attractive therapeutic candidates due to their diverse biological activities. However, existing deep learning-based sequence design models, such as ProteinMPNN, are primarily optimized using cross-entropy loss and often overlook the unique topological constraints of cyclic peptides. This limits…
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A significant advancement in Merrifield’s classic solid-phase peptide synthesis (SPPS) that greatly expands the scope of accessible peptide structures is reported here. Building upon the one-bead, one-compound concept, this approach enables the simultaneous synthesis of multiple peptides on a single bead, followed by a…
David Herrmann, Patrick Hodapp, Martin Starman, Pei-Chi Huang + 16 more
Analytical data in chemistry and other disciplines is usually generated in different formats and lacks common data and metadata standards that are necessary for a FAIR handling of research data. In the work presented herein, we describe a workflow that uses non-standardized, in some cases proprietary data formats from…
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This paper presents GLAS (Git-based Lab Automated Scheduler or Get Lab Automation Simplified), an open-source, robust, and highly expandable Git-based architecture designed for laboratory automation. GLAS can be deployed in both partially and fully automated experimental science laboratories, enabling the development…
Riley Hickman, Malcolm Sim, Sergio Pablo-García, Ivan Woolhouse + 6 more
Self-driving laboratories (SDLs) are next-generation research and development platforms for closed-loop, autonomous experimentation that combine ideas from artificial intelligence, robotics, and high-performance computing. A critical component of SDLs is the decision-making algorithm used to prioritize experiments to…
Alexander S. Shved, Blake E. Ocampo, Elena S. Burlova, Casey L. Olen + 2 more
The construction, management and analysis of large in silico molecular libraries is critical in many areas of modern chemistry. Herein, we introduce the MOLecular LIibrary toolkit, "molli", which is a Python 3 cheminformatics module that provides a streamlined interface for manipulating large in silico libraries.…
E. Dalles Keyes, Marcus C. Mifflin, Maxwell J. Austin, Brighton J. Alvey + 4 more
Inspired by Nature's wide range of oxidation-induced modifications to install cross-links and cycles at tyrosine (Tyr) and other phenol-containing residue side chains, we report a Tyr-selective strategy for the preparation of Tyr-linked cyclic peptides. This approach leverages N4-substituted 1,2,4 triazoline-3,5-diones…
Frances Smith, Rhys Griffiths, Declan Meehan, Harriet Knowles + 4 more
Synthetic methods that enable the macrocyclisation of peptides facilitate the development of more effective therapeutic and diagnostic tools. Herein we report a peptide cyclisation strategy based on intramolecular interception of visible-light-mediated cysteine desulfurisation. This method allows cyclisation of…
Andrew Simmonett, Bernard Brooks, Thomas Darden
Evaluation of noncovalent electrostatic interactions is the dominant bottleneck in classical molecular dynamics simulations, and evaluation of Coulombic matrix elements similarly limits quantum mechanical self consistent field calculations. These difficulties are a result of the Coulomb operator’s slow decay, which…
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Automated chemistry platforms hold the potential to enable large-scale organic synthesis campaigns, such as producing a library of compounds for biological evaluation. The efficiency of such platforms will depend on the schedule according to which the synthesis operations are executed. In this work, we study the…