Tobin R. Sosnick, PhD

My research program involves synergistic studies of protein folding and design, protein-RNA interactions, phosphorylation, signaling, and function 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 lab employs a range of experimental and computational methods including hydrogen exchange (HX), NMR, small-angle X-ray scattering (SAXS), rapid mixing methods, mass spectrometry, molecular dynamics and home-grown coarse-grain folding simulations and modeling. I am a very a strong believer in collaboration, having co-mentored over twenty students and post-doctoral fellows who produce over 60 papers in the last 20 years. I have a history of developing multi-approaches to bear on a problem. Since my Ph.D. in low temperature physics in 1989, I have entered many different areas, including delineating protein and RNA folding pathways and denatured states, de novo structure prediction, and the design of light-sensitive allosteric proteins.

Harvard University
Cambridge
Ph.D. - Applied Physics
1989

University of California
San Diego
B.A. - Physics
1983

Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation.
Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation. Int J Mol Sci. 2023 Jan 31; 24(3).
PMID: 36768981

LILAC: enhanced actin imaging with an optogenetic Lifeact.
LILAC: enhanced actin imaging with an optogenetic Lifeact. Nat Methods. 2023 02; 20(2):214-217.
PMID: 36717692

Development of in vivo HDX-MS with applications to a TonB-dependent transporter and other proteins.
Development of in vivo HDX-MS with applications to a TonB-dependent transporter and other proteins. Protein Sci. 2022 09; 31(9):e4402.
PMID: 36040258

HDX-MS performed on BtuB in E. coli outer membranes delineates the luminal domain's allostery and unfolding upon B12 and TonB binding.
HDX-MS performed on BtuB in E. coli outer membranes delineates the luminal domain's allostery and unfolding upon B12 and TonB binding. Proc Natl Acad Sci U S A. 2022 05 17; 119(20):e2119436119.
PMID: 35549554

Challenges and Advantages of Accounting for Backbone Flexibility in Prediction of Protein-Protein Complexes.
Challenges and Advantages of Accounting for Backbone Flexibility in Prediction of Protein-Protein Complexes. J Chem Theory Comput. 2022 Mar 08; 18(3):2016-2032.
PMID: 35213808

Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein.
Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein. Proc Natl Acad Sci U S A. 2022 01 04; 119(1).
PMID: 34969836

Engineered Metal-Binding Sites to Probe Protein Folding Transition States: Psi Analysis.
Engineered Metal-Binding Sites to Probe Protein Folding Transition States: Psi Analysis. Methods Mol Biol. 2022; 2376:31-63.
PMID: 34845602

Prediction and Validation of a Protein's Free Energy Surface Using Hydrogen Exchange and (Importantly) Its Denaturant Dependence.
Prediction and Validation of a Protein's Free Energy Surface Using Hydrogen Exchange and (Importantly) Its Denaturant Dependence. J Chem Theory Comput. 2022 Jan 11; 18(1):550-561.
PMID: 34936354

Folding and misfolding of potassium channel monomers during assembly and tetramerization.
Folding and misfolding of potassium channel monomers during assembly and tetramerization. Proc Natl Acad Sci U S A. 2021 08 24; 118(34).
PMID: 34413192

Molecular dynamics study of water channels in natural and synthetic amyloid-? fibrils.
Molecular dynamics study of water channels in natural and synthetic amyloid-? fibrils. J Chem Phys. 2021 Jun 21; 154(23):235102.
PMID: 34241272

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