Showing papers by "Mark Gerstein published in 1996"

Packing at the protein-water interface.

Abstract: We have determined the packing efficiency at the protein-water interface by calculating the volumes of atoms on the protein surface and nearby water molecules in 22 crystal structures. We find that an atom on the protein surface occupies, on average, a volume approximately 7% larger than an atom of equivalent chemical type in the protein core. In these calculations, larger volumes result from voids between atoms and thus imply a looser or less efficient packing. We further find that the volumes of individual atoms are not related to their chemical type but rather to their structural location. More exposed atoms have larger volumes. Moreover, the packing around atoms in locally concave, grooved regions of protein surfaces is looser than that around atoms in locally convex, ridge regions. This as a direct manifestation of surface curvature-dependent hydration. The net volume increase for atoms on the protein surface is compensated by volume decreases in water molecules near the surface. These waters occupy volumes smaller than those in the bulk solvent by up to 20%; the precise amount of this decrease is directly related to the extent of contact with the protein.

Using Iterative Dynamic Programming to Obtain Accurate Pairwise and Multiple Alignments of Protein Structures

Abstract: We show how a basic pairwise alignment procedure can be improved to more accurately align conserved structural regions, by using variable, position-dependent gap penalties that depend on secondary structure and by taking the consensus of a number of suboptimal alignments. These improvements, which are novel for structural alignment, are direct analogs of what is possible with normal sequences alignment. They are feasible for us since our basic structural alignment procedure, unlike others, is so similar to normal sequence alignment. We further present preliminary results that show how our procedure can be generalized to produce a multiple alignment of a family of structures. Our approach is based on finding a "median" structure from doing all possible pairwise alignments and then aligning everything to it.

Keeping the shape but changing the charges: A simulation study of urea and its iso-steric analogs

Abstract: As a first step in simulating solvent denaturation, we compare two possible potentials for urea; one based directly on a parameterization for proteins and another generated from ab initio, quantum calculations. Our results, which are derived from numerous, 1 ns simulations, indicate that both potentials reproduce essentially the same observed water structure (as evident in radial distribution functions). However, even though the quantum potential better approximates dimer energies, it is unable to simulate the dynamic behavior of water (as evident in measurements of diffusion) as well as the potential based on protein parameters. To understand its behavior in aqueous solution, we compare the urea simulations with those of solute molecules that possess the same planar, Y‐shape as urea but are progressively more hydrophobic. We find that adding urea to a solution increases the number of hydrogen bonds, while adding any of the Y‐shaped analogs decreases the number of hydrogen bonds. Moreover, in contrast to the Y‐shaped analogs, which aggregate more as they become less polar, we find that urea mixes well in solution and has little tendency to aggregate. For our analysis of aggregation, we used a novel approach based on Voronoi polyhedra as well as the traditional method of radial distribution functions. In conclusion, we discuss how urea’s unique behavior in comparison to its Y‐shaped analogs has clear implications for models of urea solvation and mechanisms of urea protein denaturation.