An outstanding challenge in computational biophysics is the simulation of a living cell at molecular detail. Over the past several years, using Stokesian Dynamics, progress has been made in simulating coarse grained molecular models of the cytoplasm. Since macromolecules comprise 20-40% of the volume of a cell, one would expect that steric interactions dominate macromolecular diffusion....
There is a need for achieving high protein concentration liquid formulations of antibody therapeutics to meet patient dose requirements. Predicting the concentrated solution behaviour requires understanding how to map protein-protein interactions on simplified models, which account for the relative contributions from repulsive and attractive forces, shape and interaction anisotropy, and any...
We are conducting continuing studies of rotational diffusion, translational diffusion, and thermodynamic compressibility of the eye lens protein bovine gammaB crystallin at low and intermediate protein concentrations. For nuclear magnetic resonance (NMR) measurements, 15N-labeled bovine gammaB crystallin was produced in transformed E Coli by recombinant means, and isolated using size-exclusion...
The talk will present an introduction to x-ray photon correlation spectroscopy (XPCS) and the specific issues associated with XPCS measurements on biological macromolecules. This will include flux requirements and methods to ameliorate beam damage. XPCS measurements of the dynamics of concentrated suspension of eye-lens proteins will be presented. The measured time correlation functions...
X-ray photon correlation spectroscopy (XPCS) measures nanoscale dynamics in real time by correlations of X-ray speckle patterns. The speckle patterns yield access to density-density correlation functions and also to higher order correlation functions. However, the highly intense X-ray beams of modern storage rings are also the cause for considerable radiation damage to the samples....
Translational diffusion of macromolecules in cell is generally assumed to be anomalous due high macromolecular crowding of the milieu. Red blood cells are a special case of cells filled quasi exclusively (95 % of the dry weight of the cell) with an almost spherical protein: hemoglobin. Hemoglobin diffusion has since a long time been recognized as facilitating the rate of oxygen diffusion...
In a dense and crowded environment such as the cell, an individual protein feels the presence of surrounding proteins. It is thus expected that direct and hydrodynamic interactions strongly affect the diffusion of proteins. Examples are suspensions of eye lens proteins, where a dramatic slow down of the local short-time diffusion of γB-crystallin and a dynamical arrest is observed...
The function of the eye is dependent on a transparent, optically refractive, and deformable eye lens. These specific physical properties are realized by a crowded multicomponent mixture of mainly crystallin proteins within the cells in the eye lens. The underlying biophysical mechanisms are not only of fundamental interest, but highly relevant to better understand and treat eye conditions such...
