2,551 research outputs found
Computation of protein geometry and its applications: Packing and function prediction
This chapter discusses geometric models of biomolecules and geometric
constructs, including the union of ball model, the weigthed Voronoi diagram,
the weighted Delaunay triangulation, and the alpha shapes. These geometric
constructs enable fast and analytical computaton of shapes of biomoleculres
(including features such as voids and pockets) and metric properties (such as
area and volume). The algorithms of Delaunay triangulation, computation of
voids and pockets, as well volume/area computation are also described. In
addition, applications in packing analysis of protein structures and protein
function prediction are also discussed.Comment: 32 pages, 9 figure
Alpha, Betti and the Megaparsec Universe: on the Topology of the Cosmic Web
We study the topology of the Megaparsec Cosmic Web in terms of the
scale-dependent Betti numbers, which formalize the topological information
content of the cosmic mass distribution. While the Betti numbers do not fully
quantify topology, they extend the information beyond conventional cosmological
studies of topology in terms of genus and Euler characteristic. The richer
information content of Betti numbers goes along the availability of fast
algorithms to compute them.
For continuous density fields, we determine the scale-dependence of Betti
numbers by invoking the cosmologically familiar filtration of sublevel or
superlevel sets defined by density thresholds. For the discrete galaxy
distribution, however, the analysis is based on the alpha shapes of the
particles. These simplicial complexes constitute an ordered sequence of nested
subsets of the Delaunay tessellation, a filtration defined by the scale
parameter, . As they are homotopy equivalent to the sublevel sets of
the distance field, they are an excellent tool for assessing the topological
structure of a discrete point distribution. In order to develop an intuitive
understanding for the behavior of Betti numbers as a function of , and
their relation to the morphological patterns in the Cosmic Web, we first study
them within the context of simple heuristic Voronoi clustering models.
Subsequently, we address the topology of structures emerging in the standard
LCDM scenario and in cosmological scenarios with alternative dark energy
content. The evolution and scale-dependence of the Betti numbers is shown to
reflect the hierarchical evolution of the Cosmic Web and yields a promising
measure of cosmological parameters. We also discuss the expected Betti numbers
as a function of the density threshold for superlevel sets of a Gaussian random
field.Comment: 42 pages, 14 figure
Shortest Geometric Paths Analysis in Structural Biology
The surface of a macromolecule, such as a protein, represents the contact point of any interaction that molecule has with solvent, ions, small molecules or other macromolecules. Analyzing the surface of macromolecules has a rich history but analyzing the distances from this surface to other surfaces or volumes has not been extensively explored. Many important questions can be answered quantitatively through these analyses. These include: what is the depth of a pocket or groove on the surface? what is the overall depth of the protein? how deeply are atoms buried from the surface? where are the tunnels in a protein? where are the pockets and what are their shapes? A single algorithm to solve one graph problem, namely Dijkstra’s shortest paths algorithm, forms the basis for algorithms to answer these many questions. Many distances can be measured, for instance the distance from the convex hull to the molecular surface while avoiding the interior of the surface is defined as Travel Depth. Alternatively, the distance from the surface to every atom can be measured, giving a measure of the Burial Depth of given residues. Measuring the minimum distance to the protein surface for all points in solvent, combined with topological guidance, allows tunnels to be located. Analyzing the surface from the deepest Travel Depth upwards allows pockets to be catalogued over the entire protein surface for additional shape analysis. Ligand binding sites in proteins are significantly deep, though this does not affect the binding affinity. Hyperthermostable proteins have a less deep surface but bury atoms more deeply, forming more spherical shapes than their mesophilic counterparts. Tunnels through proteins can be identified, for the first time tunnels that are winding or bifurcated can be analyzed. Pockets can be found all over the protein surface and these pockets can be tracked through time series, mutational series, or over protein families. All of these results are new and for the first time provide quantitative and statistical verification of some previous hypotheses about protein shape
Origin of Scaling Behavior of Protein Packing Density: A Sequential Monte Carlo Study of Compact Long Chain Polymers
Single domain proteins are thought to be tightly packed. The introduction of
voids by mutations is often regarded as destabilizing. In this study we show
that packing density for single domain proteins decreases with chain length. We
find that the radius of gyration provides poor description of protein packing
but the alpha contact number we introduce here characterize proteins well. We
further demonstrate that protein-like scaling relationship between packing
density and chain length is observed in off-lattice self-avoiding walks. A key
problem in studying compact chain polymer is the attrition problem: It is
difficult to generate independent samples of compact long self-avoiding walks.
We develop an algorithm based on the framework of sequential Monte Carlo and
succeed in generating populations of compact long chain off-lattice polymers up
to length . Results based on analysis of these chain polymers suggest
that maintaining high packing density is only characteristic of short chain
proteins. We found that the scaling behavior of packing density with chain
length of proteins is a generic feature of random polymers satisfying loose
constraint in compactness. We conclude that proteins are not optimized by
evolution to eliminate packing voids.Comment: 9 pages, 10 figures. Accepted by J. Chem. Phy
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