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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103426-24
Application #
9267989
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Resat, Haluk
Project Start
1997-05-06
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
24
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Engineering (All Types)
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Miao, Yinglong; Huang, Yu-Ming M; Walker, Ross C et al. (2018) Ligand Binding Pathways and Conformational Transitions of the HIV Protease. Biochemistry 57:1533-1541
Zhang, Jingbo; Wang, Nuo; Miao, Yinglong et al. (2018) Identification of SLAC1 anion channel residues required for CO2/bicarbonate sensing and regulation of stomatal movements. Proc Natl Acad Sci U S A 115:11129-11137
Klein, Tobias; Autin, Ludovic; Kozlikova, Barbora et al. (2018) Instant Construction and Visualization of Crowded Biological Environments. IEEE Trans Vis Comput Graph 24:862-872
Olson, Arthur J (2018) Perspectives on Structural Molecular Biology Visualization: From Past to Present. J Mol Biol 430:3997-4012
Erdemir, Ahmet; Hunter, Peter J; Holzapfel, Gerhard A et al. (2018) Perspectives on Sharing Models and Related Resources in Computational Biomechanics Research. J Biomech Eng 140:
Gaieb, Zied; Liu, Shuai; Gathiaka, Symon et al. (2018) D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies. J Comput Aided Mol Des 32:1-20
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

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