Related ArticlesCharacterization of the free-energy landscapes of proteins by NMR-guided metadynamics.
Proc Natl Acad Sci U S A. 2013 Apr 9;
Authors: Granata D, Camilloni C, Vendruscolo M, Laio A
Abstract
The use of free-energy landscapes rationalizes a wide range of aspects of protein behavior by providing a clear illustration of the different states accessible to these molecules, as well as of their populations and pathways of interconversion. The determination of the free-energy landscapes of proteins by computational methods is, however, very challenging as it requires an extensive sampling of their conformational spaces. We describe here a technique to achieve this goal with relatively limited computational resources by incorporating nuclear magnetic resonance (NMR) chemical shifts as collective variables in metadynamics simulations. As in this approach the chemical shifts are not used as structural restraints, the resulting free-energy landscapes correspond to the force fields used in the simulations. We illustrate this approach in the case of the third Ig-binding domain of protein G from streptococcal bacteria (GB3). Our calculations reveal the existence of a folding intermediate of GB3 with nonnative structural elements. Furthermore, the availability of the free-energy landscape enables the folding mechanism of GB3 to be elucidated by analyzing the conformational ensembles corresponding to the native, intermediate, and unfolded states, as well as the transition states between them. Taken together, these results show that, by incorporating experimental data as collective variables in metadynamics simulations, it is possible to enhance the sampling efficiency by two or more orders of magnitude with respect to standard molecular dynamics simulations, and thus to estimate free-energy differences among the different states of a protein with a kBT accuracy by generating trajectories of just a few microseconds.
PMID: 23572592 [PubMed - as supplied by publisher]
[NMR paper] A NMR guided approach for CsrA-RNA crystallization.
A NMR guided approach for CsrA-RNA crystallization.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles A NMR guided approach for CsrA-RNA crystallization.
J Biomol NMR. 2013 Jan 29;
Authors: Koharudin LM, Boelens R, Kaptein R, Gronenborn AM
Abstract
Structure determination of protein-nucleic acid complexes remains a challenging task. Here we present a simple method for generating crystals of a CsrA-nucleic acid complex, guided entirely by results from...
The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation
The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation
Available online 13 December 2012
Publication year: 2012
Source:Current Opinion in Structural Biology</br>
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Historically it has been virtually impossible to experimentally determine the contribution of residual protein entropy to fundamental protein activities such as the binding of ligands. Recent progress has illuminated the possibility of employing NMR relaxation methods to quantitatively determine the role of changes in conformational...
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02-03-2013 10:13 AM
Single-shot NMR measurement of protein unfolding landscapes
Single-shot NMR measurement of protein unfolding landscapes
June 2012
Publication year: 2012
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1824, Issue 6</br>
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The transient unfolding events from the native state of a protein towards higher energy states can be closely investigated by studying the process of hydrogen exchange. Here, we present BLUU-Tramp (Biophysics Laboratory University of Udine—Temperature ramp), a new method to measure the rates for the exchange process and the underlying equilibrium thermodynamic parameters, using...
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Site-specific free energy changes in proteins upon ligand binding by NMR: Ca(2+) -displacement by Ln(3+) in a Ca(2+) -binding protein from Entamoeba histolytica.
Site-specific free energy changes in proteins upon ligand binding by NMR: Ca(2+) -displacement by Ln(3+) in a Ca(2+) -binding protein from Entamoeba histolytica.
Site-specific free energy changes in proteins upon ligand binding by NMR: Ca(2+) -displacement by Ln(3+) in a Ca(2+) -binding protein from Entamoeba histolytica.
Chem Biol Drug Des. 2011 Jan 14;
Authors: Chandra K, Mustafi SM, Muthukumar S, Chary KV
The study of protein-ligand interaction has been of a great interest in contemporary structural biology. The understanding of the nature...
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01-18-2011 10:22 PM
[NMR paper] Free-energy calculations highlight differences in accuracy between X-ray and NMR stru
Free-energy calculations highlight differences in accuracy between X-ray and NMR structures and add value to protein structure prediction.
Related Articles Free-energy calculations highlight differences in accuracy between X-ray and NMR structures and add value to protein structure prediction.
Structure. 2001 Oct;9(10):905-16
Authors: Lee MR, Kollman PA
BACKGROUND: While X-ray crystallography structures of proteins are considerably more reliable than those from NMR spectroscopy, it has been difficult to assess the inherent accuracy of NMR...
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11-19-2010 08:44 PM
[NMR paper] The pressure-temperature free energy-landscape of staphylococcal nuclease monitored b
The pressure-temperature free energy-landscape of staphylococcal nuclease monitored by (1)H NMR.
Related Articles The pressure-temperature free energy-landscape of staphylococcal nuclease monitored by (1)H NMR.
J Mol Biol. 2000 Apr 28;298(2):293-302
Authors: Lassalle MW, Yamada H, Akasaka K
The thermodynamic stability of staphylococcal nuclease was studied against the variation of both temperature and pressure by utilizing (1)H NMR spectroscopy at 750 MHz in 20 mM Mes buffer containing 99.9 % (2)H(2)O, pH 5.3. Equilibrium fractions of folded...
Characterization of the free-energy landscapes of proteins by NMR-guided metadynamics.
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