TY  - GEN
ID  - heidok5898
TI  - Crystalline Protein Dynamics : A Simulation Analysis of Staphylococcal Nuclease
KW  - Roentgen-Strukturanalyseprotein 
KW  -  molecular-dynamics 
KW  -  crystallography 
KW  -  high-pressure 
KW  -  scattering
Y1  - 2005///
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/5898/
AV  - public
N2  - Understanding motions in protein crystals is likely to furnish insight into functional protein dynamics and will improve models for refinement against diffraction data. In this thesis, molecular dynamics (MD) simulations of crystalline Staphylococcal nuclease are reported and analysed in terms of fluctuations, correlations, X-ray diffuse scattering, disorder and models of protein motion. Convergence properties of dynamical quantities are determined. The logarithmic dependence on the simulation length of the R factor with the experimental X-ray diffuse scattering, which is determined by the atomic displacement variance-covariance matrix, is extrapolated to predict a convergence time for the whole variance-covariance matrix of approximately 1 microsecond. The dynamical origin of the X-ray diffuse scattering is investigated using models of liquid-like and collective motion. A smooth, nearly-isotropic scattering shell at q=0.28Ang^-1 originates from equal contributions from correlations in nearest-neighbour water molecule dynamics and from internal protein motions, the latter consisting of alpha-helix pitch and inter-beta-strand fluctuations. Superposed on the shell are intense features that originate from a very small number of slowly-varying (>10ns) collective motions. The individual features are assigned to specific collective motions in the protein, and some of these describe potentially functional active-site deformations. The dynamics along each collective mode is described using Brownian dynamics. Modes with frequencies below 0.55THz are overdamped while the majority (98.6%) of modes perfom underdamped vibrations. MD simulations over the pressure range 1bar to 15kbar reveal a qualitative change in the internal protein motions at approximately 4kbar. This change involves the existence of two linear regimes in the mean-square displacement for internal protein motion with a twofold decrease in the slope above 4kbar. The major effect of the pressure increase on the dynamics is a loss of  large-amplitude, collective protein modes below 2THz effective frequency.
A1  - Meinhold, Lars
ER  -