Donna Bassolino-Klimas

The limiting behavior of water hydrating a phospholipid monolayer: A computer simulation study

We report molecular dynamics simulations of water hydrating a lipid (dimyristoylphosphatidylcholine) monolayer under conditions chosen to eliminate simulation artifacts. These simulations provide a description of the behavior of the membrane–water interface that agrees with recent experimental studies. In particular, we find that the hydrating water orients to contribute the positive end of its dipole to the substantially positive electrostatic potential of the membrane interior, consistent with interpretations of recent experiments. In addition, recent experiments show that this water reorients rapidly on the NMR time scale. Our results concur, however the relatively rapid water motion does not preclude the preferential ordering that we observe. The limiting behavior of the system shows three hydration shells about the lipid PC headgroups and significant hydrogen bonding of water to the phosphate groups. The choline group experiences different environments, and the structure of the first hydration shell ...

Analysis of the three-dimensional antigenic structure of giant ragweed allergen, Amb t 5

The ragweed allergens Amb t 5 and Amb a 5 are among the smallest inhaled protein allergens known, containing a single, immunodominant T-cell epitope. In this study we analyzed the B-cell epitope structure of Amb t 5. The three-dimensional structures of Amb t 5 and Amb a 5 have been determined by NMR spectroscopy, providing a rare opportunity to analyze three-dimensional antigenic sites. Amb t 5 residues likely to be important for antigenicity were identified by examining the surface area of Amb t 5 accessible to a probe of the size of an antibody molecule. After changing these residues to the corresponding Amb a 5 residues, recombinant proteins were purified and tested for loss of antigenic activity. Inhibition radio-immunoassays, using sera from 8 individuals who had received immunotherapy with giant ragweed extract, allowed the mutations to be divided into three groups: (1) mutations that had little or no effect on antibody binding, (2) mutations that caused a loss of antigenic activity to a different degree in different sera and (3) mutations that drastically reduced antigenic activity in all sera tested. This last set of mutations clustered in the third loop of Amb t 5, suggesting that antibody recognition of Amb t 5, like T-cell recognition, is primarily directed towards a single, immunodominant site.

Supercomputing Studies of Biomembranes

Although computer simulation of biological molecules has seen widespread growth and is widely accepted as an important biochemical tool, it is hampered by lim ited computing resources. Biomolecular systems, by necessity, contain a large number of interaction sites. In many cases, these sites interact over quite large dis tances. Further, the time scales of biological interest are long, which requires that simulations of dynamical properties at the atomic level must be lengthy to ade quately probe these motions. We address these issues through discussions of atomic-level molecular dynam ics simulations of biological lipid bilayer membranes, which are key constructs in biochemistry. These simu lations reproduce many experimental observables and provide a degree of resolution currently unavailable experimentally. The lengths of these simulations, the longest of which was 2 nanoseconds, were sufficient to effectively sample many of the motions governing the behavior of biomembranes. Examples are given showing the importance of long-range interactions. The number of interaction sites required by these sim ulations is discussed, particularly the need for explicit representation of solvent molecules.