Visible Volume: a Robust Measure for Protein Structure Characterization

We propose a new characterization of protein structure based on the natural tetrahedral geometry of the β carbon and a new geometric measure of structural similarity, called visible volume. In our model, the side-chains are replaced by an ideal tetrahedron, the orientation of which is fixed with respect to the backbone and corresponds to the preferred rotamer directions. Visible volume is a measure of the non-occluded empty space surrounding each residue position after the side-chains have been removed. It is a robust, parameter-free, locally-computed quantity that accounts for many of the spatial constraints that are of relevance to the corresponding position in the native structure. When computing visible volume, we ignore the nature of both the residue observed at each site and the ones surrounding it. We focus instead on the space that, together, these residues could occupy. By doing so, we are able to quantify a new kind of invariance beyond the apparent variations in protein families, namely, the conservation of the physical space available at structurally equivalent positions for side-chain packing. Corresponding positions in native structures are likely to be of interest in protein structure prediction, protein design, and homology modeling. Visible volume is related to the degree of exposure of a residue position and to the actual rotamers in native proteins. In this article, we discuss the properties of this new measure, namely, its robustness with respect to both crystallographic uncertainties and naturally occurring variations in atomic coordinates, and the remarkable fact that it is essentially independent of the choice of the parameters used in calculating it. We also show how visible volume can be used to align protein structures, to identify structurally equivalent positions that are conserved in a family of proteins, and to single out positions in a protein that are likely to be of biological interest. These properties qualify visible volume as a powerful tool in a variety of applications, from the detailed analysis of protein structure to homology modeling, protein structural alignment, and the definition of better scoring functions for threading purposes.

Unicast-based Characterization of Network Loss Topologies

Current Internet transport protocols make end-to-end measurements and maintain per-connection state to regulate the use of shared network resources. When a number of such connections share a common endpoint, that endpoint has the opportunity to correlate these end-to-end measurements to better diagnose and control the use of shared resources. A valuable characterization of such shared resources is the "loss topology". From the perspective of a server with concurrent connections to multiple clients, the loss topology is a logical tree rooted at the server in which edges represent lossy paths between a pair of internal network nodes. We develop an end-to-end unicast packet probing technique and an associated analytical framework to: (1) infer loss topologies, (2) identify loss rates of links in an existing loss topology, and (3) augment a topology to incorporate the arrival of a new connection. Correct, efficient inference of loss topology information enables new techniques for aggregate congestion control, QoS admission control, connection scheduling and mirror site selection. Our extensive simulation results demonstrate that our approach is robust in terms of its accuracy and convergence over a wide range of network conditions.