NBCR will develop new computational technologies to create stronger, clearer connections across diverse scales of biological organization ~ from molecules to whole-organ systems. We will develop new modeling paradigms, tools, technologies, and corresponding expertise to bring the crossing of scales into routine practice, leveraging a new era in biomedical science already enriched by a wide variety of types, sizes, and sources of data. To achieve these goals, we plan to pursue activities in four parallel core project areas: To achieve these goals, we plan to pursue activities in four parallel core project areas: " Core 1 will advance technologies for atomic-to-subcellular simulation and discovery to enable investigation of large-scale biological systems with unprecedented accuracy and transform current state-of- the-art computational capabilities approaching the mesoscale. " Core 2 will focus on creating a flexible model assembly environment for cells and subcellular scenes, facilitating incorporation of data from multiple methods and the capability of connecting into various simulation engines, thus enabling crossing from molecular to cellular scales for individual cells and cells in tissues. " Core 3 will expand its interactive and extensible multi-scale modeling environment connected with a publicly available database containing experimental data, models, and model components with improved methods to more tightly integrate coupling between physiological scales that range from the molecular (with Cores 1 and 2) to whole-organ. " Core 4 will focus on practical cyber-infrastructure, which unites all the cores and the various requisite computing elements to provide a framework that enables routine and effective use of ubiquitous and increasingly diverse computational and data architectures. Our proposal describes a coordinated development plan among the four cores, in close collaboration with Driving Biomedical Project investigators, that will harness the data deluge to develop insights from detailed structural models, develop and probe computational multi-scale functional models, and create and disseminate robust, reusable workflows that will make seamless integration across scales routine practice in biomedical research.
We will develop new multi-scale computing technologies that will enable investigations to cross diverse scales of biological organization to create greater insight into biomedical science. The technologies to be developed will have broad impact on basic biomedical research, cancer, infectious diseases, bacterial infection, heart disease, neurodegenerative disease, and patient-specific modeling, with direct translational impact on clinical health care.
|Schilling, Jan M; Horikawa, Yousuke T; Zemljic-Harpf, Alice E et al. (2016) Electrophysiology and metabolism of caveolin-3-overexpressing mice. Basic Res Cardiol 111:28|
|Yang, Longhua; Skjevik, Ã…ge A; Han Du, Wen-Ge et al. (2016) Data for molecular dynamics simulations of B-type cytochrome c oxidase with the Amber force field. Data Brief 8:1209-14|
|Swift, Robert V; Jusoh, Siti A; Offutt, Tavina L et al. (2016) Knowledge-Based Methods To Train and Optimize Virtual Screening Ensembles. J Chem Inf Model 56:830-42|
|Goldgof, Gregory M; Durrant, Jacob D; Ottilie, Sabine et al. (2016) Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor. Sci Rep 6:27806|
|Yang, Longhua; Skjevik, Ã…ge A; Han Du, Wen-Ge et al. (2016) Water exit pathways and proton pumping mechanism in B-type cytochrome c oxidase from molecular dynamics simulations. Biochim Biophys Acta 1857:1594-606|
|Im, Wonpil; Liang, Jie; Olson, Arthur et al. (2016) Challenges in structural approaches to cell modeling. J Mol Biol 428:2943-64|
|Lee, Christopher T; Comer, Jeffrey; Herndon, Conner et al. (2016) Simulation-Based Approaches for Determining Membrane Permeability of Small Compounds. J Chem Inf Model 56:721-33|
|Schiffer, Jamie M; Feher, Victoria A; Malmstrom, Robert D et al. (2016) Capturing Invisible Motions in the Transition from Ground to Rare Excited States of T4 Lysozyme L99A. Biophys J 111:1631-1640|
|Zhang, Yanhang; Barocas, Victor H; Berceli, Scott A et al. (2016) Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention. Ann Biomed Eng 44:2642-60|
|Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael et al. (2016) Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study. J Phys Chem B 120:8264-75|
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