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Critical Review of Published Papers in Bio-Neutron Scattering

Neutron scattering is an open access technique, which is provided by large scale facilities such as the FRM 2 in Garching. Inelastic neutron scattering yields information on fast molecular motions such as protein structural fluctuations and hydration water on a pico to nano-second time scale comparable to MD simulations. To honor their work on MD simulations of proteins, the Nobel Prize in Chemistry in 2013 was devoted to M. Karplus, M. Levitt and A. Warshel.

A common method to compare simulation and experiment involves hydrated proteins (low solvent signal) and elastic scattering experiments ref.
One of the basic parameters is the molecular mean square displacement investigated versus temperature and instrumental resolution. The latter defines the observation time scale of relevant molecular processes. At a particular onset temperature one observes an "anharmonic enhancement" of motional amplitudes, suggesting a thermal softening of the elastic structural properties, often denoted as the "protein dynamical transition" PDT . At more advanced stages of analysis, correlation times and the geometry of molecular motions can be deduced.
Below we present a critical discussion of relevant papers of the field. The figure compares published data of elastic protein mean square displacements (dx^2) versus temperature of D2O-hydrated myoglobin.
The various changes in the T-dependence of the displacements can be assigned to different molecular processes: CH3: side chain rotational transition become resolved. The transition assigned to PDT denotes the protein dynamical transition, motions coupled to hydration water, depending on the degree hydration (red more, blue less water, green: PDT analysis).
To perform meaningful experiments requires, besides understanding the technique (nuclear physics), a combined knowledge of condensed matter physics, biophysics and molecular biology. A typical "user" often does not have this kind of expertise.

Here I present a critical review of selected publications in historical order for pedagogical reasons.
Comments to:

2016: Workshop "50 years of neutron backscattering spectroscopy"

Protein Dynamical Transition from Backscattering Displacements

2015: Spurious Pressure Effects on Protein Dynamics

Influence of Pressure and Crowding on the Subnanosecond Dynamics of Globular Proteins, by M. Erlkamp, J. Marion, N. Martinez, C. Czeslik, J. Peters and R. Winter J.Phys.Chem B 119 4842(2015). Comment

2014: Does a dry protein undergo a glass transition?

Does a dry protein undergo a glass transition by A. Frontzek, S. Strokov, ,J. Embs and S. Lushnikov J.Phys.Chem B 118(11) 2791-2802(2014). Comment

2012/3: Two step scenario of the protein dynamical transition

Change of caged dynamics of hydrated proteins by Capaccioli, Ngai, Ancherbak, Paciaroni, J. Chem.Phys. 138 (2013) 235102. Comment

Evidence of coexistence of change of caged dynamics.. by Capaccioli, Ngai, Paciaroni, J.Phys. Chem. B 116 (2012) 1745. Comment rejected by Editor of JPCB

2011: The RENS puzzle

Elastic incoherent neutron scattering operating by varying instrumental energy resolution: Principle, simulations, and experiments of the resolution elastic neutron scattering (RENS) S. Magazu, F. Migliardo, A. Benedetto Review of Scientific Instruments 82 (10), 105115 (2011)
nearly identical: Magazu, Migliardo, Benedetto, Vertessy in Chemical Physics 424(2013)26: Protein dynamics and neutron scattering..

Protein dynamical transition at 110 K, by C. Kim, M. Tate and S. Gruner PNAS 108, 20897 (2011) Comment

2011: The Frauenfelder Mössbauer effect and the PDT
Mössbauer effect in proteins, Young, Frauenfelder, Fenimore, PRL(2011)107, 158102 Comment

2008: Elliptical protein phase diagrams
Pressure and temperature dependent protein stability by Widersich, Skerra, Köhler, Friedrich, PNAS 105, 575 (2008) Comment

2006: Instrumental resolution effects interpreted as a fragile-strong crossover
Observation of fragile to strong dynamic cross-over of protein hydration water by S.H. Chen, L.Liu, E. Fratini, P. Bagliaoni, A. Faraone and E. Mamontov, PNAS USA 103, 9012 (2006) Comment

2004: Frauenfelders alpha/beta relaxation
Bulk solvent and hydration shell fluctuations by Fenimore, Frauenfelder, Mc Mahon, Young PNAS USA (2004)101,14408 Comment

2003: Hydrogen Distributions
Hydrogen atoms in proteins, Engler, Ostermann, Nijmura, Parak, PNAS USA (2003)100,10243 Comment

2002: Slaving II
Solvent fluctuations dominate protein dynamics and function by Fenimore, Frauenfelder, Mc Mahon, Parak, PNAS USA (2002)99,16047 Comment

2002: Confined water and the two simple explanation
A model for water motion in crystals of lysozyme based on an incoherent quasi-elastic neutron scattering study by C.Bon, A.J. Dianoux, M. Ferrand and M.S. Lehmann, Biophys. J. 83( 2002) 1578 Comment

The protein dynamical transition may have a simple explanantion
by M. R. Daniel, J. Finney and J. Smith, Faraday Discussion (2002) 122,163

2000: Protein force constants from elastic displacements?
How soft is a protein? A protein dynamics force constant measured by neutron scattering by J. Zaccai, Science 288,1604( 2000) Comment

1998: Dynamic labelling of different functional parts of BR
by V. Reat, H. Patzelt, M. Ferrand, C. Pfister, D. Oesterhelt, G. Zaccai PNAS 95(1998)4970 Comment
1998: Activity below the transition?
Enzyme Activity below the Protein Dynamical Transition at 220K by R. Daniel, J.Smith, M. Ferrand, S. Hery, R. Dunn, J. Finney, Biophys. J. 75 (1998) 2504 Comment

1993: Melting of a frozen protein solution
Thermal motion and function of bacteriorhodopsin in purple membrane, effect of temperature and hydration observed by neutron scattering by M. Ferrand, A. Dianoux, W. Petry an G. Zaccai, PNAS 90, 9668 (1993)communicated by Hans Frauenfelder. Comment

1992: Confined water (I):
Single particle dynamics of hydration water in protein, M.C. Bellissent-Funel, J. Teixera, J.F. Bradley, S.H. Chen and L. Crespi, Physica B 181 &181, 740 (1992). Comment

1991: Review Article on MD Simulation and Experiments
Protein Dynamics: comparison of simulations with inelastic neutron scattering experiments, by J. Smith, Quat. Rev. Biophys.24 (1991), 227 Comment
1991: Frauenfelders Energy Landscape
The energy landscapes and motions in proteins, H. Frauenfelder, S. Sligar and P. Wolynes, Science 254 (1991) 1598 Comment

1990: Vacuum simulation of a hydrated protein
Dynamics of myoglobin: comparison of simulation results with neutron scattering spectra, by J. Smith, K. Kuczera and M. Karplus, PNAS USA (1990)87, 1601. Comment

The temperature dependence of dynamics of hydrated myoglobin, comparison of force field calculations with neutron scattering data by R. Loncharich and B. Brooks, J. Mol. Biol. (1990)215, 439,

1989: first spectral analysis of protein dynamics:
Dynamical transition of myoglobin revealed by inelastic neutron scattering, W. Doster, W. Petry and S. Cusack, Nature 337,754(1989)

Internal dynamics of globular proteins, comparison of neutron scattering measurements and theoretical models by J. Smith, K. Kuczera, B. Tidor, W. Doster, S.Cusack and M. Karplus, Physica B(1989) 156, 437.

1982: Ligand Binding to Hexokinase
Inelastic neutron scattering analysis of hexokinase dynamics and its modification on binding of glucose by B. Jacrot, S. Cusack, A. Dianoux and D. Engelman, Nature 300 (1982)84

1980/1996: spurious oscillations of hydration water jump rate
Molecular dynamics of hydrated proteins, H. Middendorf, J. Randall and A. J. Leadbetter, Phil. Trans. R. Soc. Lond.B. (1980) 290, 639. and Middendorf, Phys. B. 226, 113 (1996)

last changes: Sept. 4th, 2016