The reductionist paradigm insists that the physicochemical behavior of proteins can eventually be simulated if enough details of the molecular physics are included in the model. At the moment, however, completely atomistic simulations are very computationally time-consuming for even an individual biomolecule and are ill-suited for surveying the behavior of entire families of biomolecules. Fortunately, many (but not all!) of the aspects of biomolecular dynamics are sufficiently collective in their origin so that the relevant dynamics can be understood with coarse-grained models that capture the global characteristics of the energy landscape while still perhaps being inaccurate in some fine grained details of the landscape. Although we may sacrifice precision when using coarse grained models, they allow us to sample the entire configuration space, allowing accurate determinations of free energy surfaces and accurate statistics that relate to experimental observables, difficult to access with present day all-atom simulations.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM071862-08
Application #
8627179
Study Section
Special Emphasis Panel (ZRG1-BCMB-D)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
8
Fiscal Year
2014
Total Cost
$426,375
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Wang, Zhipeng; Potoyan, Davit A; Wolynes, Peter G (2018) Stochastic resonances in a distributed genetic broadcasting system: the NF?B/I?B paradigm. J R Soc Interface 15:
Ramirez-Sarmiento, Cesar A; Komives, Elizabeth A (2018) Hydrogen-deuterium exchange mass spectrometry reveals folding and allostery in protein-protein interactions. Methods 144:43-52
Ferreiro, Diego U; Komives, Elizabeth A; Wolynes, Peter G (2018) Frustration, function and folding. Curr Opin Struct Biol 48:68-73
Narang, Dominic; Chen, Wei; Ricci, Clarisse G et al. (2018) RelA-Containing NF?B Dimers Have Strikingly Different DNA-Binding Cavities in the Absence of DNA. J Mol Biol 430:1510-1520
Wang, Zhipeng; Potoyan, Davit A; Wolynes, Peter G (2018) Modeling the therapeutic efficacy of NF?B synthetic decoy oligodeoxynucleotides (ODNs). BMC Syst Biol 12:4
Ramsey, Kristen M; Narang, Dominic; Komives, Elizabeth A (2018) Prediction of the presence of a seventh ankyrin repeat in I?B? from homology modeling combined with hydrogen-deuterium exchange mass spectrometry (HDX-MS). Protein Sci 27:1624-1635
Dembinski, Holly E; Wismer, Kevin; Vargas, Jesse D et al. (2017) Functional importance of stripping in NF?B signaling revealed by a stripping-impaired I?B? mutant. Proc Natl Acad Sci U S A 114:1916-1921
Potoyan, Davit A; Bueno, Carlos; Zheng, Weihua et al. (2017) Resolving the NF?B Heterodimer Binding Paradox: Strain and Frustration Guide the Binding of Dimeric Transcription Factors. J Am Chem Soc 139:18558-18566
Potoyan, Davit A; Wolynes, Peter G (2017) Stochastic dynamics of genetic broadcasting networks. Phys Rev E 96:052305
Ramsey, Kristen M; Dembinski, Holly E; Chen, Wei et al. (2017) DNA and I?B? Both Induce Long-Range Conformational Changes in NF?B. J Mol Biol 429:999-1008

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