TY  - JOUR
AU  - Smolin, N.
AU  - Biehl, R.
AU  - Kneller, G.B.
AU  - Richter, D.
AU  - Smith, J.C.
TI  - Functional domain motions in proteins on the 1 - 100 ns timescale: Comparison of neutron spin echo spectroscopy of phosphoglycerate kinase with molecular dynamics simulation
JO  - Biophysical journal
VL  - 102
SN  - 0006-3495
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - PreJuSER-20685
SP  - 1108 - 1117
PY  - 2012
N1  - 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.
AB  - 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.
KW  - Diffusion
KW  - Molecular Dynamics Simulation
KW  - Movement
KW  - Neutron Diffraction: methods
KW  - Phosphoglycerate Kinase: chemistry
KW  - Phosphoglycerate Kinase: metabolism
KW  - Protein Structure, Tertiary
KW  - Rotation
KW  - Saccharomyces cerevisiae: enzymology
KW  - Scattering, Small Angle
KW  - Time Factors
KW  - Phosphoglycerate Kinase (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:22404933
C2  - pmc:PMC3296038
UR  - <Go to ISI:>//WOS:000301280900017
DO  - DOI:10.1016/j.bpj.2012.01.002
UR  - https://juser.fz-juelich.de/record/20685
ER  -