Introduction to Protein Structure Prediction

This chapter gives a graceful introduction to problem of protein three- dimensional structure prediction, and focuses on how to make structural sense out of a single input sequence with unknown structure, the 'query' or 'target' sequence. We give an overview of the different classes of modelling techniques, notably template-based and template free. We also discuss the way in which structural predictions are validated within the global com- munity, and elaborate on the extent to which predicted structures may be trusted and used in practice. Finally we discuss whether the concept of a sin- gle fold pertaining to a protein structure is sustainable given recent insights. In short, we conclude that the general protein three-dimensional structure prediction problem remains unsolved, especially if we desire quantitative predictions. However, if a homologous structural template is available in the PDB model or reasonable to high accuracy may be generated

The scheduling techniques of ESP2

The Mission Analysis Division of the Systems Analysis and Integration Laboratory at the Marshall Space Flight Center has developed a robust automatic scheduler which can produce detailed schedules for the multi-step activities required for payload operations on the Space Station. This scheduler, a part of the Expert Scheduling Program (ESP2), has five components: the bookkeeper, checker, loader, selector, and explainer. The bookkeeper maintains the usage profiles for nondepletable resources, consumables, equipment, crew, and the times of all the steps for the payload activities for several different schedules simultaneously. The checker searches the data maintained by the bookkeeper and finds times when the constraints of each step of an activity are satisfied. The loader is an expert system that uses the techniques of forward chaining, depth-first searching, and backtracking to manage the workings of the checker so that activities are placed in the schedule without violating constraints (such as crew, resources, and orbit opportunities). The checker searches the data maintained by the bookkeeper and finds times when the constraints of each step of an activity are satisfied. The loader is an expert system which uses the techniques of forward chaining, depth-first searching, and backtracking to manage the workings of the checker so that activities are placed in the schedule without violating the constraints. The selector has several methods of choosing the next activity for the loader to schedule. The explainer shows the user why an activity was or was not scheduled at a certain time; it offers a unique graphical explanation of how the expert system (the loader) works

Increased security through open source

In this paper we discuss the impact of open source on both the security and transparency of a software system. We focus on the more technical aspects of this issue, combining and extending arguments developed over the years. We stress that our discussion of the problem only applies to software for general purpose computing systems. For embedded systems, where the software usually cannot easily be patched or upgraded, different considerations may apply

Strategies for protein structure model generation

This chapter deals with approaches for protein three-dimensional structure prediction, starting out from a single input sequence with unknown struc- ture, the 'query' or 'target' sequence. Both template based and template free modelling techniques are treated, and how resulting structural models may be selected and refined. We give a concrete flowchart for how to de- cide which modelling strategy is best suited in particular circumstances, and which steps need to be taken in each strategy. Notably, the ability to locate a suitable structural template by homology or fold recognition is crucial; without this models will be of low quality at best. With a template avail- able, the quality of the query-template alignment crucially determines the model quality. We also discuss how other, courser, experimental data may be incorporated in the modelling process to alleviate the problem of missing template structures. Finally, we discuss measures to predict the quality of models generated

The meaning of alignment: lessons from structural diversity

<p>Abstract</p> <p>Background</p> <p>Protein structural alignment provides a fundamental basis for deriving principles of functional and evolutionary relationships. It is routinely used for structural classification and functional characterization of proteins and for the construction of sequence alignment benchmarks. However, the available techniques do not fully consider the implications of protein structural diversity and typically generate a single alignment between sequences.</p> <p>Results</p> <p>We have taken alternative protein crystal structures and generated simulation snapshots to explicitly investigate the impact of structural changes on the alignments. We show that structural diversity has a significant effect on structural alignment. Moreover, we observe alignment inconsistencies even for modest spatial divergence, implying that the biological interpretation of alignments is less straightforward than commonly assumed. A salient example is the GroES 'mobile loop' where sub-Ångstrom variations give rise to contradictory sequence alignments.</p> <p>Conclusion</p> <p>A comprehensive treatment of ambiguous alignment regions is crucial for further development of structural alignment applications and for the representation of alignments in general. For this purpose we have developed an on-line database containing our data and new ways of visualizing alignment inconsistencies, which can be found at <url>http://www.ibi.vu.nl/databases/stralivari</url>.</p

A format for the interchange of scheduling models

In recent years a variety of space-activity schedulers have been developed within the aerospace community. Space-activity schedulers are characterized by their need to handle large numbers of activities which are time-window constrained and make high demands on many scarce resources, but are minimally constrained by predecessor/successor requirements or critical paths. Two needs to exchange data between these schedulers have materialized. First, there is significant interest in comparing and evaluating the different scheduling engines to ensure that the best technology is applied to each scheduling endeavor. Second, there is a developing requirement to divide a single scheduling task among different sites, each using a different scheduler. In fact, the scheduling task for International Space Station Alpha (ISSA) will be distributed among NASA centers and among the international partners. The format used to interchange scheduling data for ISSA will likely use a growth version of the format discussed in this paper. The model interchange format (or MIF, pronounced as one syllable) discussed in this paper is a robust solution to the need to interchange scheduling requirements for space activities. It is highly extensible, human-readable, and can be generated or edited with common text editors. It also serves well the need to support a 'benchmark' data case which can be delivered on any computer platform

A Short-Cut to Testing Passage Comprehension

In this study the feasibility of administering the Woodcock Passage Comprehension Test in written rather than oral form was examined. ** In their short life the Woodcock Reading Mastery Tests (Woodcock. 1973) have quickly found wide-spread usage. A critical review of the tests by Tuinman (1978) points out various limitations to the claims made by Woodcock for his tests. but nevertheless recognizes this battery as an important and useful contribution to the field

Macroeconomic Crisis and Individual Firm Performance: The Mexican Experience

This paper considers financial, operational, solvency, and performance ratios, in order to detect when there were balance sheets’ variations related to the 1994 Mexican currency crisis. Quarterly results for 88 non-financial Mexican companies that survived the crisis are used, and tests for structural change are performed. Findings show that generally firms’ balance sheets deteriorated between the fourth quarters of 1993 and 1995, which points the possibility of corporate roots of the macroeconomic crisis. Although in most cases firms’ balance sheets improved after the crisis, the recovery was partial and gradual, and overall this episode was prejudicial even for surviving companies

From Discrete-Time Models to Continuous-Time, Asynchronous Models of Financial Markets

Most agent-based simulation models of financial markets are discrete-time in nature. In this paper, we investigate to what degree such models are extensible to continuous-time, asynchronous modelling of financial markets. We study the behaviour of a learning market maker in a market with information asymmetry, and investigate the difference caused in the market dynamics between the discrete-time simulation and continuous-time, asynchronous simulation. We show that the characteristics of the market prices are different in the two cases, and observe that additional information is being revealed in the continuous-time, asynchronous models, which can be acted upon by the agents in such models. Si