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.
|Mulero, Maria Carmen; Shahabi, Shandy; Ko, Myung Soo et al. (2018) Protein Cofactors Are Essential for High-Affinity DNA Binding by the Nuclear Factor ?B RelA Subunit. Biochemistry 57:2943-2957|
|Jurrus, Elizabeth; Engel, Dave; Star, Keith et al. (2018) Improvements to the APBS biomolecular solvation software suite. Protein Sci 27:112-128|
|Huang, Yu-Ming M; Huber, Gary A; Wang, Nuo et al. (2018) Brownian dynamic study of an enzyme metabolon in the TCA cycle: Substrate kinetics and channeling. Protein Sci 27:463-471|
|Caliman, Alisha D; Miao, Yinglong; McCammon, James A (2018) Mapping the allosteric sites of the A2A adenosine receptor. Chem Biol Drug Des 91:5-16|
|Sousa, Carole; Golebiewska, Anna; Poovathingal, Suresh K et al. (2018) Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures. EMBO Rep 19:|
|Bohl, Thomas E; Ieong, Pek; Lee, John K et al. (2018) The substrate-binding cap of the UDP-diacylglucosamine pyrophosphatase LpxH is highly flexible, enabling facile substrate binding and product release. J Biol Chem 293:7969-7981|
|Cranford, Jonathan P; O'Hara, Thomas J; Villongco, Christopher T et al. (2018) Efficient Computational Modeling of Human Ventricular Activation and Its Electrocardiographic Representation: A Sensitivity Study. Cardiovasc Eng Technol 9:447-467|
|Gilbert, Kathleen; Forsch, Nickolas; Hegde, Sanjeet et al. (2018) Atlas-Based Computational Analysis of Heart Shape and Function in Congenital Heart Disease. J Cardiovasc Transl Res 11:123-132|
|Amaro, Rommie E; Ieong, Pek U; Huber, Gary et al. (2018) A Computational Assay that Explores the Hemagglutinin/Neuraminidase Functional Balance Reveals the Neuraminidase Secondary Site as a Novel Anti-Influenza Target. ACS Cent Sci 4:1570-1577|
|Utesch, Tillmann; de Miguel Catalina, Alejandra; Schattenberg, Caspar et al. (2018) A Computational Modeling Approach Predicts Interaction of the Antifungal Protein AFP from Aspergillus giganteus with Fungal Membranes via Its ?-Core Motif. mSphere 3:|
Showing the most recent 10 out of 162 publications