Tobin R. Sosnick
My research program involves synergistic studies of protein and RNA folding, function and design, with both experimental and computational components. The research is based on the premise that rigorous and innovative studies of basic processes have broad implications in many areas of biological research. My experimental experience in protein folding, design, modeling, and biophysical methods provides an enormous benefit to our computational studies which heavily rely on the use of fundamental principles of protein folding. Since my Ph.D. in low temperature physics in 1989, I have entered many different biological fields and have made an impact in each area. These areas include delineating protein and RNA folding pathways, de novo structure prediction, design of light-triggered allosteric proteins, and RNA folding during transcription. My lab employs a range of experimental and computational methods including NMR, small-angle X-ray scattering, rapid mixing methods, hydrogen exchange, molecular dynamics and coarse-grain folding simulations. I am a very a strong believer in collaboration, having co-mentored 15+ students and post-doctoral fellows who produced 30+ papers in the last 10 years.
Factors that control the chemistry of the LOV domain photocycle. Zayner JP, Sosnick TR. (2014) PLoS ONE 9(1): e87074.
Investigating models of protein function and allostery with a widespread mutational analysis of a light-activated protein. Zayner JP, Antoniou C, French AR, Sosnick TR. (2013) Biophys J. 105(4):1027-36.
Simplified protein models: predicting folding pathways and structure using amino acid sequences. Adhikari AN, Freed KF, Sosnick TR. (2013) Phys Rev Lett. 111(2):028103.
Discovering RNA-protein interactome by using chemical context profiling of the RNA-protein interface. Parisien M, Wang X, Perdrizet G 2nd, Lamphear C, Fierke CA, Maheshwari KC, Wilde MJ, Sosnick TR, Pan T. (2013) Cell Rep. 3(5):1703-13.
De novo prediction of protein folding pathways and structure using the principle of sequential stabilization. Adhikari AN, Freed KF, Sosnick TR. (2012) Proc Natl Acad Sci U S A. 109(43):17442-7.
Context and force field dependence of the loss of protein backbone entropy upon folding using realistic denatured and native state ensembles. Baxa MC, Haddadian EJ, Jha AK, Freed KF, Sosnick TR. (2012) J Am Chem Soc. 134(38):15929-36. (Featured in JACS Spotlight)
The folding transition state of protein L is extensive with nonnative interactions (and not small and polarized). Yoo TY, Adhikari A, Xia Z, Huynh T, Freed KF, Zhou R, Sosnick TR. (2012) J Mol Biol. 420(3):220-34.
A "Link-Psi" strategy using crosslinking indicates that the folding transition state of ubiquitin is not very malleable. Shandiz AT, Baxa MC, Sosnick TR. (2012) Protein Sci. 21(6):819-27.