Protein Folding

Protein Folding

Protein Folding

We are interested in determining the transistion state of folding for many small proteins through the introduction of metal-binding sites across the surface of the protein.

Approach

  • Many small proteins fold in a cooperative fashion so that only the native state and unfolded state populate. We can deduce characteristics of the transition state by connecting changes in the folding kinetics with specific structural perturbations.
  • By measuring the relationship between kinetics and metal concentration, we can determine the contact pairs in the transition state and glean general principles in folding.

Z.P. Gates*, M.C. Baxa*, W. Yu, J.A. Riback, H. Li, B. Roux, S.B.H. Kent, T.R. Sosnick, "Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core" (in press)

W. Yu, M.C. Baxa, I. Gagnon, K.F. Freed, T.R. Sosnick, "Cooperative folding near the downhill limit determined with amino acid resolution by hydrogen exchange" Proc Natl Acad Sci U S A 113 (2016) 4747-52.

M.C. Baxa, W. Yu, A.N. Adhikari, L. Ge, Z. Xia, R. Zhou, K.F. Freed, T.R. Sosnick, "Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar" Proc Natl Acad Sci U S A 112 (2015) 8302-7.

J.J. Skinner, W. Yu, E.K. Gichana, M.C. Baxa, J.R. Hinshaw, K.F. Freed, T.R. Sosnick, "Benchmarking all-atom simulations using hydrogen exchange" Proc Natl Acad Sci U S A 111 (2014) 15975-80.

T.Y. Yoo, A. Adhikari, Z. Xia, T. Huynh, K.F. Freed, R. Zhou, T.R. Sosnick, "The folding transition state of protein L is extensive with nonnative interactions (and not small and polarized)" J Mol Biol 420 (2012) 220-34.

T.R. Sosnick, D. Barrick, "The folding of single domain proteins--have we reached a consensus?" Curr Opin Struct Biol 21 (2011) 12-24.

M.C. Baxa, K.F. Freed, T.R. Sosnick, "Psi-constrained simulations of protein folding transition states: implications for calculating φ" J Mol Biol 386 (2009) 920-8.