An exploration of opportunities for a theory of information inadequacy

Our everyday experiences show that the lack of needed information in various human affairs may give rise to consequences that we would like to avoid – e.g. the 2004 Tsunami in Southeast Asia. However, we still do not have a coherent theoretical body that addresses such experiences of information inadequacy as this changes everything in respect to the current conception of the information society, where technology plays a central role. To this end, we provide an initial exploration of opportunities for such a theory: when needed information is not available in human affairs, for any reason. We start with diagnoses of five existing central theoretical bodies that constitute promising candidates to account for instances of information inadequacy. The results show though that these do not offer a comprehensive account for situations where needed information is missing. Secondly, an empirical investigation was conducted, utilizing grounded theory approach, where fifty cases of information inadequacy were analysed. This revealed a number of patterns of plausible causes of information inadequacies in human affairs, which offer a preliminary foundation for a future theory of information inadequacy. This result suggests that information inadequacies may be understood as various instances of information-lack and information-overflow. These two, in turn, include numerous factors that cause information inadequacies, ranging from political and cultural structures, through human individual capabilities, and ending with procedural set-ups and technological artefacts. We advocate that further research should be conducted to explore various instances of information inadequacy aimed to the formulation of a coherent theory

FINDSITE LHM: A Threading-Based Approach to Ligand Homology Modeling

©2009 Brylinski, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.DOI: 10.1371/journal.pcbi.1000405The characters LHM are superscript in the title.Ligand virtual screening is a widely used tool to assist in new pharmaceutical discovery. In practice, virtual screening approaches have a number of limitations, and the development of new methodologies is required. Previously, we showed that remotely related proteins identified by threading often share a common binding site occupied by chemically similar ligands. Here, we demonstrate that across an evolutionarily related, but distant family of proteins, the ligands that bind to the common binding site contain a set of strongly conserved anchor functional groups as well as a variable region that accounts for their binding specificity. Furthermore, the sequence and structure conservation of residues contacting the anchor functional groups is significantly higher than those contacting ligand variable regions. Exploiting these insights, we developed FINDSITELHM that employs structural information extracted from weakly related proteins to perform rapid ligand docking by homology modeling. In large scale benchmarking, using the predicted anchor-binding mode and the crystal structure of the receptor, FINDSITELHM outperforms classical docking approaches with an average ligand RMSD from native of ,2.5 A° . For weakly homologous receptor protein models, using FINDSITELHM, the fraction of recovered binding residues and specific contacts is 0.66 (0.55) and 0.49 (0.38) for highly confident (all) targets, respectively. Finally, in virtual screening for HIV-1 protease inhibitors, using similarity to the ligand anchor region yields significantly improved enrichment factors. Thus, the rather accurate, computationally inexpensive FINDSITELHM algorithm should be a useful approach to assist in the discovery of novel biopharmaceuticals