Abstract
Methods of protein structure determination based on NMR chemical shifts are becoming increasingly common. The most widely used approaches adopt the molecular fragment replacement strategy, in which structural fragments are repeatedly reassembled into different complete conformations in molecular simulations. Although these approaches are effective in generating individual structures consistent with the chemical shift data, they do not enable the sampling of the conformational space of proteins with correct statistical weights. Here, we present a method of molecular fragment replacement that makes it possible to perform equilibrium simulations of proteins, and hence to determine their free energy landscapes. This strategy is based on the encoding of the chemical shift information in a probabilistic model in Markov chain Monte Carlo simulations. First, we demonstrate that with this approach it is possible to fold proteins to their native states starting from extended structures. Second, we show that the method satisfies the detailed balance condition and hence it can be used to carry out an equilibrium sampling from the Boltzmann distribution corresponding to the force field used in the simulations. Third, by comparing the results of simulations carried out with and without chemical shift restraints we describe quantitatively the effects that these restraints have on the free energy landscapes of proteins. Taken together, these results demonstrate that the molecular fragment replacement strategy can be used in combination with chemical shift information to characterize not only the native structures of proteins but also their conformational fluctuations.
PMID: 25192938 [PubMed - as supplied by publisher]
[NMR paper] Searching For Protein Binding Sites From Molecular Dynamics Simulations and Paramagnetic Fragment-based NMR Studies.
Searching For Protein Binding Sites From Molecular Dynamics Simulations and Paramagnetic Fragment-based NMR Studies.
Related Articles Searching For Protein Binding Sites From Molecular Dynamics Simulations and Paramagnetic Fragment-based NMR Studies.
Biochim Biophys Acta. 2013 Dec 26;
Authors: Bernini A, De Angelis LH, Morandi E, Spiga O, Santucci A, Assfalg M, Molinari H, Pillozzi S, Arcangeli A, Niccolai N
Abstract
Hotspot delineation on protein surfaces represents a fundamental step for targeting protein-protein interfaces....
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01-01-2014 03:05 PM
Searching For Protein Binding Sites From Molecular Dynamics Simulations and Paramagnetic Fragment-based NMR Studies
Searching For Protein Binding Sites From Molecular Dynamics Simulations and Paramagnetic Fragment-based NMR Studies
Publication date: Available online 27 December 2013
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics</br>
Author(s): Andrea Bernini , Lucia Henrici De Angelis , Edoardo Morandi , Ottavia Spiga , Annalisa Santucci , Michael Assfalg , Henriette Molinari , Serena Pillozzi , Annarosa Arcangeli , Neri Niccolai</br>
Hotspot delineation on protein surfaces represents a fundamental step for targeting protein-protein interfaces....
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12-27-2013 11:54 AM
[CNS Yahoo group] Re: Molecular replacement
Re: Molecular replacement
I once had a similar problem. In your case, the protein is fused so you know it is there. I suggest you get initial phases from the MBP molecular replacement
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02-11-2013 08:42 AM
[NMR paper] Assessment of the Use of NMR Chemical Shifts as Replica-Averaged Structural Restraints in Molecular Dynamics Simulations to Characterize the Dynamics of Proteins.
Assessment of the Use of NMR Chemical Shifts as Replica-Averaged Structural Restraints in Molecular Dynamics Simulations to Characterize the Dynamics of Proteins.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Assessment of the Use of NMR Chemical Shifts as Replica-Averaged Structural Restraints in Molecular Dynamics Simulations to Characterize the Dynamics of Proteins.
J Phys Chem B. 2013 Feb 1;
Authors: Camilloni C, Cavalli A, Vendruscolo M
Abstract
It has been recently...
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02-03-2013 10:19 AM
Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction
Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction
Abstract While chemical shifts are invaluable for obtaining structural information from proteins, they also offer one of the rare ways to obtain information about protein dynamics. A necessary tool in transforming chemical shifts into structural and dynamic information is chemical shift prediction. In our previous work we developed a method for 4D prediction of protein 1H chemical shifts in which molecular motions, the...
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02-11-2012 10:31 AM
[NMR paper] A conformational equilibrium in a protein fragment caused by two consecutive capping
A conformational equilibrium in a protein fragment caused by two consecutive capping boxes: 1H-, 13C-NMR, and mutational analysis.
Related Articles A conformational equilibrium in a protein fragment caused by two consecutive capping boxes: 1H-, 13C-NMR, and mutational analysis.
Protein Sci. 1998 Jul;7(7):1506-15
Authors: Guerois R, Cordier-Ochsenbein F, Baleux F, Huynh-Dinh T, Neumann JM, Sanson A
The conformational properties of an 18 residues peptide spanning the entire sequence, L1KTPA5QFDAD10ELRAA15MKG, of the first helix (A-helix) of...
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11-17-2010 11:15 PM
Using NMR Chemical Shifts as Structural Restraints in Molecular Dynamics Simulations
Using NMR Chemical Shifts as Structural Restraints in Molecular Dynamics Simulations of Proteins.
Related Articles Using NMR Chemical Shifts as Structural Restraints in Molecular Dynamics Simulations of Proteins.
Structure. 2010 Aug 11;18(8):923-933
Authors: Robustelli P, Kohlhoff K, Cavalli A, Vendruscolo M
We introduce a procedure to determine the structures of proteins by incorporating NMR chemical shifts as structural restraints in molecular dynamics simulations. In this approach, the chemical shifts are expressed as differentiable...
Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts.
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