Publications

Abstract not provided.

Semiconductor bridges (SCBs) are commonly used as initiators for explosive and pyrotechnic devices. Their advantages include reduced voltage and energy requirements and exceptional safety features. Moreover, the design of systems which implement SCBs can be expedited using electrical simulation software. Successful use of this software requires that certain parameters be correctly chosen. In this paper, we explain how these parameters can be identified using optimization. We describe the problem focusing on the application of a direct optimization method for its solution, and present some numerical results.

Abstract not provided.

We have developed a novel approach to modeling the transmembrane spanning helical bundles of integral membrane proteins using only a sparse set of distance constraints, such as those derived from MS3-D, dipolar-EPR and FRET experiments. Algorithms have been written for searching the conformational space of membrane protein folds matching the set of distance constraints, which provides initial structures for local conformational searches. Local conformation search is achieved by optimizing these candidates against a custom penalty function that incorporates both measures derived from statistical analysis of solved membrane protein structures and distance constraints obtained from experiments. This results in refined helical bundles to which the interhelical loops and amino acid side-chains are added. Using a set of only 27 distance constraints extracted from the literature, our methods successfully recover the structure of dark-adapted rhodopsin to within 3.2 {angstrom} of the crystal structure.

APPSPACK is software for solving unconstrained and bound constrained optimization problems. It implements an asynchronous parallel pattern search method that has been specifically designed for problems characterized by expensive function evaluations. Using APPSPACK to solve optimization problems has several advantages: No derivative information is needed; the procedure for evaluating the objective function can be executed via a separate program or script; the code can be run in serial or parallel, regardless of whether or not the function evaluation itself is parallel; and the software is freely available. We describe the underlying algorithm, data structures, and features of APPSPACK version 4.0 as well as how to use and customize the software.

We present a two-step approach to modeling the transmembrane spanning helical bundles of integral membrane proteins using only sparse distance constraints, such as those derived from chemical cross-linking, dipolar EPR and FRET experiments. In Step 1, using an algorithm, we developed, the conformational space of membrane protein folds matching a set of distance constraints is explored to provide initial structures for local conformational searches. In Step 2, these structures refined against a custom penalty function that incorporates both measures derived from statistical analysis of solved membrane protein structures and distance constraints obtained from experiments. We begin by describing the statistical analysis of the solved membrane protein structures from which the theoretical portion of the penalty function was derived. We then describe the penalty function, and, using a set of six test cases, demonstrate that it is capable of distinguishing helical bundles that are close to the native bundle from those that are far from the native bundle. Finally, using a set of only 27 distance constraints extracted from the literature, we show that our method successfully recovers the structure of dark-adapted rhodopsin to within 3.2 Å of the crystal structure.