Galaxy is a mature, browser accessible workbench for scientific computing. It enables scientists to share, analyze and visualize their own data, with minimal technical impediments. A thriving global community continues to use, maintain and contribute to the project, with support from multiple national infrastructure providers that enable freely accessible analysis and training services. The Galaxy Training Network supports free, self-directed, virtual training with >230 integrated tutorials. Project engagement metrics have continued to grow over the last 2 years, including source code contributions, publications, software packages wrapped as tools, registered users and their daily analysis jobs, and new independent specialized servers. Key Galaxy technical developments include an improved user interface for launching large-scale analyses with many files, interactive tools for exploratory data analysis, and a complete suite of machine learning tools. Important scientific developments enabled by Galaxy include Vertebrate Genome Project (VGP) assembly workflows and global SARS-CoV-2 collaborations.

Thermoresponsive polymers can change structure or solubility as a function of temperature. Block co-polymers of polyethers have a response that depends on polymer molecular weight and co-polymer composition. A coarse-grained model for aqueous polyethers is developed and applied to polyethylene oxide and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock co-polymers. In this model, no interaction sites on hydrogen atoms are included, no Coulombic interactions are present, and all interactions are short-ranged, treated with a combination of twoand three-body terms. Our simulations find that The triblock co-polymers tend to associate at temperatures above 350 K. The aggregation is stabilized by contact between The hydrophobic methyl groups on The propylene oxide monomers and involves a large, favorable change in entropy.

Polypeptoids differ from polypeptides in that the amide bond can more frequently adopt both cis and trans conformations. The transition between the two conformations requires overcoming a large energy barrier, making it difficult for conventional molecular simulations to adequately visit the cis and trans structures. A replica-exchange method is presented that allows for easy rotations of the amide bond and also an efficient linking to a high temperature replica. The method allows for just three replicas (one at the temperature and Hamiltonian of interest, a second high temperature replica with a biased dihedral potential, and a third connecting them) to overcome the amide bond sampling problem and also enhance sampling for other coordinates. The results indicate that for short peptoid oligomers, the conformations can range from all cis to all trans with an average cis/trans ratio that depends on side chain and potential model.

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The helicase protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is both a good potential drug target and very flexible. The flexibility, and therefore its function, could be reduced through knowledge of these motions and identification of allosteric pockets. Using molecular dynamics simulations with enhanced sampling, we determined key modes of motion and sites on the protein that are at the interface between flexible domains of the proteins. We developed an approach to map the principal components of motion onto the surface of a potential binding pocket to help in the identification of allosteric sites.