NDLI: On the precision of experimentally determined protein folding rates and φ-values

Content Provider	PubMed Central
Author	Rios, Miguel A. De Los Muralidhara, B. K. Wildes, David Sosnick, Tobin R. Marqusee, Susan Wittung-stafshede, Pernilla Plaxco, Kevin W. Ingo, Ruczinski
Abstract	φ-Values, a relatively direct probe of transition-state structure, are an important benchmark in both experimental and theoretical studies of protein folding. Recently, however, significant controversy has emerged regarding the reliability with which φ-values can be determined experimentally: Because φ is a ratio of differences between experimental observables it is extremely sensitive to errors in those observations when the differences are small. Here we address this issue directly by performing blind, replicate measurements in three laboratories. By monitoring within- and between-laboratory variability, we have determined the precision with which folding rates and φ-values are measured using generally accepted laboratory practices and under conditions typical of our laboratories. We find that, unless the change in free energy associated with the probing mutation is quite large, the precision of φ-values is relatively poor when determined using rates extrapolated to the absence of denaturant. In contrast, when we employ rates estimated at nonzero denaturant concentrations or assume that the slopes of the chevron arms (m f and m u ) are invariant upon mutation, the precision of our estimates of φ is significantly improved. Nevertheless, the reproducibility we thus obtain still compares poorly with the confidence intervals typically reported in the literature. This discrepancy appears to arise due to differences in how precision is calculated, the dependence of precision on the number of data points employed in defining a chevron, and interlaboratory sources of variability that may have been largely ignored in the prior literature.
Related Links	http://dx.doi.org/10.1110/ps.051870506
Ending Page	563
Page Count	11
Starting Page	553
File Format	PDF
ISSN	09618368
e-ISSN	1469896X
Journal	Protein Science : A Publication of the Protein Society
Issue Number	3
Volume Number	15
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2006-02-01
Access Restriction	Open
Rights Holder	Cold Spring Harbor Laboratory Press
Subject Keyword	Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Some recommendations for the practitioner to improve the precision of experimentally determined protein folding rates and Φ values

On the precision of experimentally determined protein folding rates and phi-values.

Some recommendations for the practitioner to improve the precision of experimentally determined protein folding rates and phi values.

Predicting repeat protein folding kinetics from an experimentally determined folding energy landscape

Characterisation of transition state structures for protein folding using ‘high’, ‘medium’ and ‘low’ Φ-values

The effects of nonnative interactions on protein folding rates: Theory and simulation

An experimentally determined protein folding energy landscape

Relationship of Leffler (Brønsted) α values and protein folding Φ values to position of transition-state structures on reaction coordinates

Predicting repeat protein folding kinetics from an experimentally determined folding energy landscape.

On the precision of experimentally determined protein folding rates and φ-values

Similar Documents

Some recommendations for the practitioner to improve the precision of experimentally determined protein folding rates and Φ values

On the precision of experimentally determined protein folding rates and phi-values.

Some recommendations for the practitioner to improve the precision of experimentally determined protein folding rates and phi values.

Predicting repeat protein folding kinetics from an experimentally determined folding energy landscape

Characterisation of transition state structures for protein folding using ‘high’, ‘medium’ and ‘low’ Φ-values

The effects of nonnative interactions on protein folding rates: Theory and simulation

An experimentally determined protein folding energy landscape

Relationship of Leffler (Brønsted) α values and protein folding Φ values to position of transition-state structures on reaction coordinates

Predicting repeat protein folding kinetics from an experimentally determined folding energy landscape.

On the precision of experimentally determined protein folding rates and φ-values