The paper presents new developments and amendments to the ATSAS package (version 2.4) for processing and analysis of isotropic small-angle scattering data.

We present a method for reconstructing a 3D structure from a pair distribution function by flexibly fitting known x-ray structures toward a conformation that agrees with the low-resolution data. This method uses a linear combination of low-frequency normal modes from elastic-network description of the molecule in an iterative manner to deform the structure optimally to conform to the target pair distribution function. A simple function, pair distance distribution function between atoms, is chosen as a test model to establish computational algorithms-optimization algorithm and scoring function-that can utilize low-resolution 1D data. To select a correct structural model based on less information, we developed a scoring function that takes into account a characteristic of pair distribution functions. In addition, we employ a new optimization algorithm, the trusted region method, that relies on both first and second derivatives of the scoring function. Illustrative results of our studies on simulated 1D data from five different proteins, for which large conformational changes are known to occur, are presented.

Engineered nanoparticles have been designed based on the self-assembling properties of synthetic coiled-coil lipopeptide building blocks. The presence of an isoleucine zipper within the lipopeptide together with the aggregating effects of an N-terminal lipid drives formation of 20-25 nm nanoparticles in solution. Biophysical studies support a model in which the lipid is buried in the centre of the nanoparticle, with 20-30 trimeric helical coiled-coil bundles radiating out into solution. A promiscuous T-helper epitope and a synthetic B-cell epitope mimetic derived from the circumsporozoite protein of Plasmodium falciparum have been linked to each lipopeptide chain, with the result that 60-90 copies of each antigen are displayed over the surface of the nanoparticle. These nanoparticles elicit strong humoral immune responses in mice and rabbits, including antibodies able to cross-react with the parasite, thereby, supporting the potential value of this delivery system in synthetic vaccine design.

Simulations were performed for up to 150 simplified spherical horse heart cytochrome c molecules in the presence of a charged surface, which serves as an approximate model for a lipid membrane. Screened electrostatic and short-ranged attractive as well as repulsive van der Waals forces for interparticle and particle-membrane interactions are utilized in the simulations. At a distance from the membrane, where particle-membrane interactions are negligible, the simulation is coupled to a noninteraction continuum analogous to a heat bath [Geyer et al., J. Chem. Phys. 120, 4573 (2004)]. From the particles' density profiles perpendicular to the planar surface binding isotherms are derived and compared to experimental results [Heimburg et al. (1999)]. Using a negatively charged structureless membrane surface a saturation effect was found for relatively large particle concentrations. Since biological membranes often contain membrane proteins, we also studied the influence of additional charges on our model membrane mimicking bacterial reaction centers. We find that the onset of the saturation occurs for much lower concentrations and is sensitive to the detailed implementation. Therefore we suggest that local distortion of membrane planarity (undulation), or lipid demixing, or the presence of charged integral membrane proteins create preferential binding sites on the membrane. Only then do we observe saturation at physiological concentrations.

We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures. This method uses a linear combination of low-frequency normal modes from an elastic network description of the molecule in an iterative manner to deform the structure to conform optimally to the target pair distribution function derived from SAXS data. For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained. In this paper, we demonstrate the validity of our coarse-graining approach to study SAXS data. Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented.