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

Challenges and Advantages of Accounting for Backbone Flexibility in Prediction of Protein-Protein Complexes.
Faruk NF, Peng X, Freed KF, Roux B, Sosnick TR. 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.
Gaffney KA, Guo R, Bridges MD, Muhammednazaar S, Chen D, Kim M, Yang Z, Schilmiller AL, Faruk NF, Peng X, Jones AD, Kim KH, Sun L, Hubbell WL, Sosnick TR, Hong H. 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.
Baxa MC, Sosnick TR. 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.
Peng X, Baxa M, Faruk N, Sachleben JR, Pintscher S, Gagnon IA, Houliston S, Arrowsmith CH, Freed KF, Rocklin GJ, Sosnick TR. 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.
Song KC, Molina AV, Chen R, Gagnon IA, Koh YH, Roux B, Sosnick TR. 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-ß fibrils.
Natesh SR, Hummels AR, Sachleben JR, Sosnick TR, Freed KF, Douglas JF, Meredith SC, Haddadian EJ. Molecular dynamics study of water channels in natural and synthetic amyloid-ß fibrils. J Chem Phys. 2021 Jun 21; 154(23):235102.
PMID: 34241272

Properties of protein unfolded states suggest broad selection for expanded conformational ensembles.
Bowman MA, Riback JA, Rodriguez A, Guo H, Li J, Sosnick TR, Clark PL. Properties of protein unfolded states suggest broad selection for expanded conformational ensembles. Proc Natl Acad Sci U S A. 2020 09 22; 117(38):23356-23364.
PMID: 32879005

Water as a Good Solvent for Unfolded Proteins: Folding and Collapse are Fundamentally Different.
Clark PL, Plaxco KW, Sosnick TR. Water as a Good Solvent for Unfolded Proteins: Folding and Collapse are Fundamentally Different. J Mol Biol. 2020 04 17; 432(9):2882-2889.
PMID: 32044346

Structural basis for adhesion G protein-coupled receptor Gpr126 function.
Leon K, Cunningham RL, Riback JA, Feldman E, Li J, Sosnick TR, Zhao M, Monk KR, Araç D. Structural basis for adhesion G protein-coupled receptor Gpr126 function. Nat Commun. 2020 01 10; 11(1):194.
PMID: 31924782

On the Interpretation of Force-Induced Unfolding Studies of Membrane Proteins Using Fast Simulations.
Wang Z, Jumper JM, Freed KF, Sosnick TR. On the Interpretation of Force-Induced Unfolding Studies of Membrane Proteins Using Fast Simulations. Biophys J. 2019 10 15; 117(8):1429-1441.
PMID: 31587831

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