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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-D (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
La Jolla
United States
Zip Code
Wolynes, Peter G (2015) Evolution, energy landscapes and the paradoxes of protein folding. Biochimie 119:218-30
Potoyan, Davit A; Wolynes, Peter G (2014) On the dephasing of genetic oscillators. Proc Natl Acad Sci U S A 111:2391-6
Alverdi, Vera; Hetrick, Byron; Joseph, Simpson et al. (2014) Direct observation of a transient ternary complex during I?B?-mediated dissociation of NF-?B from DNA. Proc Natl Acad Sci U S A 111:225-30
Tao, Zhihua; Fusco, Amanda; Huang, De-Bin et al. (2014) p100/I?B? sequesters and inhibits NF-?B through kappaBsome formation. Proc Natl Acad Sci U S A 111:15946-51
Schafer, N P; Kim, B L; Zheng, W et al. (2014) Learning To Fold Proteins Using Energy Landscape Theory. Isr J Chem 54:1311-1337
Dembinski, Holly; Wismer, Kevin; Balasubramaniam, Deepa et al. (2014) Predicted disorder-to-order transition mutations in I?B? disrupt function. Phys Chem Chem Phys 16:6480-5
Alves, Bryce N; Tsui, Rachel; Almaden, Jonathan et al. (2014) I?B? is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner. J Immunol 192:3121-32
Ferreiro, Diego U; Komives, Elizabeth A; Wolynes, Peter G (2014) Frustration in biomolecules. Q Rev Biophys 47:285-363
Kim, Bobby L; Schafer, Nicholas P; Wolynes, Peter G (2014) Predictive energy landscapes for folding ?-helical transmembrane proteins. Proc Natl Acad Sci U S A 111:11031-6
Cervantes, Carla F; Handley, Lindsey D; Sue, Shih-Che et al. (2013) Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IýýBýý. J Mol Biol 425:902-13

Showing the most recent 10 out of 58 publications