Acquisition of Unix Computer Cluster for Molecular Dynamics Simulation Calculations

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PROJECT SUMMARY In response to NOT-GM-22-017, Notice of Special Interest: Administrative Supplements for Equipment Purchases for Select NIGMS-Funded Awards, we request funds to upgrade our local Unix compute cluster, which was purchased in 2012, with GPU nodes that are needed for the calculations described on the parent grant. Our parent grant aims to understand the formation of non-enveloped organelles and condensates. Many calculations of smaller size arise and are hampered by writing supercomputing proposals. The current nodes are nearly impossible to maintain due to changes in hardware compatibility. Our calculations focus on deciphering the thermodynamic manifold, enthalpic versus entropic driving forces, underlying the solubility limit and consequent phase transition associated with the formation of condensates.1 We also investigate the role of compositional/sequence dependencies and protein disorder2 on the formation and stability of these assemblies. Design of therapeutic targets that promote or inhibit formation of component proteins or nucleic acids in biomolecular condensates requires a detailed understanding of the molecular forces that drive their formation or dissolution. We will consider model mixtures relevant to cell signaling consisting of pentapeptides GGXGG, GGpXGG, and GXGXG systems, where X is serine, threonine, and tyrosine, to model the compositional dependency on condensate formation. We will also study the mitochondrial Cox17 protein where the level of disorder is controlled by physiological conditions.3 This 60 aa protein is an ideal system to test our insights from the small pentapeptide model studies.