ϕ-Value Analysis for Ultrafast Folding Proteins by NMR Relaxation Dispersion Academic Article

abstract

• Proteins that fold rapidly, on the (sub-) microsecond time scale, offer the prospect of direct comparison between experimental data and molecular dynamics simulations. However, experimental studies for such proteins frequently are hindered because folding rates are too fast to measure using conventional stopped-flow methods. To overcome this impediment, NMR spin relaxation dispersion experiments are used to quantify mutational effects on kinetics (DeltaDeltaG(o)), stability (DeltaDeltaG(o)), and phi-values (DeltaDeltaG(dagger)/DeltaDeltaG(o)) for proteins exhibiting chemical exchange line broadening that is fast on the NMR chemical shift time scale. The accuracy of phi-value analysis is enhanced because mutational effects on denatured or intermediate states can be detected through changes in line broadening. The transition and intermediate states of the villin headpiece domain, HP67, are characterized in varying solvent conditions to validate the method.

authors

• Cho, Jae

author list (cited authors)

• Cho, J., O'Connell, N., Raleigh, D. P., & Palmer, A. G.

citation count

• 18

complete list of authors

• Cho, Jae-Hyun||O'Connell, Nichole||Raleigh, Daniel P||Palmer, Arthur G

publication date

• January 2009

publisher

• American Chemical Society (ACS)  Publisher

published in

• Journal of the American Chemical Society  Journal

keywords

• Magnetic Resonance Spectroscopy
• Protein Folding
• Proteins
• Thermodynamics

Digital Object Identifier (DOI)

• 10.1021/ja909052h

start page

• 450

end page

• 451

volume

• 132

issue

• 2

URL

• http://dx.doi.org/10.1021/ja909052h