Journal Article

PreJuSER-20685

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Functional domain motions in proteins on the 1 - 100 ns timescale: Comparison of neutron spin echo spectroscopy of phosphoglycerate kinase with molecular dynamics simulation

Smolin, N. ; Biehl, R.FZJ* ; Kneller, G. B. ; Richter, D.FZJ* ; Smith, J. C.

2012
Rockefeller Univ. Press New York, NY

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Please use a persistent id in citations: doi:10.1016/j.bpj.2012.01.002

Abstract: Protein function often requires large-scale domain motion. An exciting new development in the experimental characterization of domain motions in proteins is the application of neutron spin-echo spectroscopy (NSE). NSE directly probes coherent (i.e., pair correlated) scattering on the ~1-100 ns timescale. Here, we report on all-atom molecular-dynamics (MD) simulation of a protein, phosphoglycerate kinase, from which we calculate small-angle neutron scattering (SANS) and NSE scattering properties. The simulation-derived and experimental-solution SANS results are in excellent agreement. The contributions of translational and rotational whole-molecule diffusion to the simulation-derived NSE and potential problems in their estimation are examined. Principal component analysis identifies types of domain motion that dominate the internal motion's contribution to the NSE signal, with the largest being classic hinge bending. The associated free-energy profiles are quasiharmonic and the frictional properties correspond to highly overdamped motion. The amplitudes of the motions derived by MD are smaller than those derived from the experimental analysis, and possible reasons for this difference are discussed. The MD results confirm that a significant component of the NSE arises from internal dynamics. They also demonstrate that the combination of NSE with MD is potentially useful for determining the forms, potentials of mean force, and time dependence of functional domain motions in proteins.

Keyword(s): Diffusion (MeSH) ; Molecular Dynamics Simulation (MeSH) ; Movement (MeSH) ; Neutron Diffraction: methods (MeSH) ; Phosphoglycerate Kinase: chemistry (MeSH) ; Phosphoglycerate Kinase: metabolism (MeSH) ; Protein Structure, Tertiary (MeSH) ; Rotation (MeSH) ; Saccharomyces cerevisiae: enzymology (MeSH) ; Scattering, Small Angle (MeSH) ; Time Factors (MeSH) ; Phosphoglycerate Kinase ; J

Note: The research was sponsored by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract No. DE-AC05-00OR22725. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under contract No. DE-AC02-05CH11231.

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Contributing Institute(s):

1. Neutronenstreuung (ICS-1)
2. Neutronenstreuung (JCNS-1)

Research Program(s):

1. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (FUEK505) (FUEK505)
2. 544 - In-house Research with PNI (POF2-544) (POF2-544)

Experiment(s):

1. KWS-2: Small angle scattering diffractometer (NL3ao)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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