Abstract
Multidomain proteins with two or more independently folded functional domains are prevalent in nature. Whereas most multidomain proteins are linked linearly in sequence, roughly one-tenth possess domain insertions where a guest domain is implanted into a loop of a host domain, such that the two domains are connected by a pair of interdomain linkers. Here, we characterized the influence of the interdomain linkers on the structure and dynamics of a domain-insertion protein in which the guest LysM domain is inserted into a central loop of the host CVNH domain. Expanding upon our previous crystallographic and NMR studies, we applied SAXS in combination with NMR paramagnetic relaxation enhancement to construct a structural model of the overall two-domain system. Although the two domains have no fixed relative orientation, certain orientations were found to be preferred over others. We also assessed the accuracies of molecular mechanics force fields in modeling the structure and dynamics of tethered multidomain proteins by integrating our experimental results with microsecond-scale atomistic molecular dynamics simulations. In particular, our evaluation of two different combinations of the latest force fields and water models revealed that both combinations accurately reproduce certain structural and dynamical properties, but are inaccurate for others. Overall, our study illustrates the value of integrating experimental NMR and SAXS studies with long timescale atomistic simulations for characterizing structural ensembles of flexibly linked multidomain systems.
Magic Angle Spinning NMR Spectroscopy Guided Atomistic Characterization of Structure and Dynamics in HIV-1 Protein Assemblies
Magic Angle Spinning NMR Spectroscopy Guided Atomistic Characterization of Structure and Dynamics in HIV-1 Protein Assemblies
Publication date: Available online 19 December 2017
Source:Current Opinion in Colloid & Interface Science</br>
Author(s): Rupal Gupta, Tatyana Polenova</br>
Since its discovery, human immunodeficiency virus (HIV) has been an intense subject of research. Several biophysical methodologies have aided towards understanding of the viral lifecycle and infectivity. Magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy has...
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12-19-2017 11:31 AM
Integrating NOE and RDC using sum-of-squares relaxation for protein structure determination
Integrating NOE and RDC using sum-of-squares relaxation for protein structure determination
Abstract
We revisit the problem of protein structure determination from geometrical restraints from NMR, using convex optimization. It is well-known that the NP-hard distance geometry problem of determining atomic positions from pairwise distance restraints can be relaxed into a convex semidefinite program (SDP). However, often the NOE distance restraints are too imprecise and sparse for accurate structure determination. Residual dipolar coupling (RDC)...
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06-15-2017 03:26 AM
[NMR paper] CryoEM Structure Refinement by Integrating NMR Chemical Shifts with Molecular Dynamics Simulations.
CryoEM Structure Refinement by Integrating NMR Chemical Shifts with Molecular Dynamics Simulations.
Related Articles CryoEM Structure Refinement by Integrating NMR Chemical Shifts with Molecular Dynamics Simulations.
J Phys Chem B. 2017 Feb 09;:
Authors: Perilla JR, Zhao G, Lu M, Ning J, Hou G, Byeon IL, Gronenborn AM, Polenova T, Zhang P
Abstract
Single particle cryoEM has emerged as a powerful method for structure determination of proteins and complexes, complementing X-ray crystallography and NMR spectroscopy. Yet, for many...
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02-10-2017 04:19 PM
Liquid state DNP at high magnetic fields: Instrumentation, experimental results and atomistic modelling by molecular dynamics simulations
From The DNP-NMR Blog:
Liquid state DNP at high magnetic fields: Instrumentation, experimental results and atomistic modelling by molecular dynamics simulations
Prisner, T., V. Denysenkov, and D. Sezer, Liquid state DNP at high magnetic fields: Instrumentation, experimental results and atomistic modelling by molecular dynamics simulations. J Magn Reson, 2016. 264: p. 68-77.
http://www.ncbi.nlm.nih.gov/pubmed/26920832
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05-05-2016 03:15 AM
[NMR paper] Integrating solid-state NMR and computational modeling to investigate the structure and dynamics of membrane-associated ghrelin.
Integrating solid-state NMR and computational modeling to investigate the structure and dynamics of membrane-associated ghrelin.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.plosone.org-images-pone_120x30.png http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Integrating solid-state NMR and computational modeling to investigate the structure and dynamics of membrane-associated ghrelin.
PLoS One. 2015;10(3):e0122444
Authors: ...
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02-18-2016 08:10 PM
[NMR paper] Probing the Interaction between cHAVc3 Peptide and the EC1 Domain of E-cadherin using NMR and Molecular Dynamics Simulations.
Probing the Interaction between cHAVc3 Peptide and the EC1 Domain of E-cadherin using NMR and Molecular Dynamics Simulations.
Related Articles Probing the Interaction between cHAVc3 Peptide and the EC1 Domain of E-cadherin using NMR and Molecular Dynamics Simulations.
J Biomol Struct Dyn. 2016 Jan 5;:1-48
Authors: Alaofi A, Farokhi E, Prasasty VD, Anbanandam A, Kuczera K, Siahaan TJ
Abstract
The goal of this work is to probe the interaction between cyclic cHAVc3 peptide and the EC1 domain of human E-cadherin protein. Cyclic...
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01-07-2016 08:36 AM
Structure and Dynamics of Intermediate Protein States by NMR and Simulations
Structure and Dynamics of Intermediate Protein States by NMR and Simulations
Publication date: 28 January 2014
Source:Biophysical Journal, Volume 106, Issue 2, Supplement 1</br>
Author(s): Alfonso De Simone</br>
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01-29-2014 12:50 AM
[NMR paper] Unique Structure and Dynamics of the EphA5 Ligand Binding Domain Mediate Its Binding Specificity as Revealed by X-ray Crystallography, NMR and MD Simulations.
Unique Structure and Dynamics of the EphA5 Ligand Binding Domain Mediate Its Binding Specificity as Revealed by X-ray Crystallography, NMR and MD Simulations.
Unique Structure and Dynamics of the EphA5 Ligand Binding Domain Mediate Its Binding Specificity as Revealed by X-ray Crystallography, NMR and MD Simulations.
PLoS One. 2013;8(9):e74040
Authors: Huan X, Shi J, Lim L, Mitra S, Zhu W, Qin H, Pasquale EB, Song J
Abstract
The 16 EphA and EphB receptors represent the largest family of receptor tyrosine kinases, and their interactions...
Integrating NMR, SAXS, and Atomistic Simulations: Structure and Dynamics of a Two-Domain Protein.
Linear Mode
