Publication Date:
2015-09-26
Description:
Experimental, theoretical, and computational studies of small proteins suggest that interresidue contacts not present in the folded structure play little or no role in the self-assembly mechanism. Non-native contacts can, however, influence folding kinetics by introducing additional local minima that slow diffusion over the global free-energy barrier between folded and unfolded states. Here, we combine single-molecule fluorescence with all-atom molecular dynamics simulations to discover the structural origin for the slow diffusion that markedly decreases the folding rate for a designed alpha-helical protein. Our experimental determination of transition path times and our analysis of the simulations point to non-native salt bridges between helices as the source, which provides a quantitative glimpse of how specific intramolecular interactions influence protein folding rates by altering dynamics and not activation free energies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Hoi Sung -- Piana-Agostinetti, Stefano -- Shaw, David E -- Eaton, William A -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1504-10. doi: 10.1126/science.aab1369.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-0520, USA. chunghoi@niddk.nih.gov stefano.piana-agostinetti@DEShawResearch.com david.shaw@DEShawResearch.com eaton@helix.nih.gov. ; D. E. Shaw Research, New York, NY 10036, USA. chunghoi@niddk.nih.gov stefano.piana-agostinetti@DEShawResearch.com david.shaw@DEShawResearch.com eaton@helix.nih.gov. ; D. E. Shaw Research, New York, NY 10036, USA. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. chunghoi@niddk.nih.gov stefano.piana-agostinetti@DEShawResearch.com david.shaw@DEShawResearch.com eaton@helix.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404828" target="_blank"〉PubMed〈/a〉
Keywords:
Diffusion
;
Entropy
;
Hydrogen-Ion Concentration
;
Kinetics
;
*Models, Chemical
;
Molecular Dynamics Simulation
;
*Protein Folding
;
Protein Structure, Secondary
;
Proteins/*chemistry
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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