Functional recycling of C2 domains throughout evolution: A comparative study of synaptotagmin, protein kinase C and phospholipase C by sequence, structural and modelling approaches

The C2 domain is one of the most frequent and widely distributed calcium-binding motifs. Its structure comprises an eight-stranded beta-sandwich with two structural types as if the result of a circular permutation. Combining sequence, structural and modelling information, we have explored, at different levels of granularity, the functional characteristics of several families of C2 domains. At the coarsest level,the similarity correlates with key structural determinants of the C2 domain fold and, at the finest level, with the domain architecture of the proteins containing them, highlighting the functional diversity between the various subfamilies. The functional diversity appears as different conserved surface patches throughout this common fold. In some cases, these patches are related to substrate-binding sites whereas in others they correspond to interfaces of presumably permanent interaction between other domains within the same polypeptide chain. For those related to substrate-binding sites, the predictions overlap with biochemical data in addition to providing some novel observations. For those acting as protein-protein interfaces' our modelling analysis suggests that slight variations between families are a result of not only complementary adaptations in the interfaces involved but also different domain architecture. In the light of the sequence and structural genomic projects, the work presented here shows that modelling approaches along with careful sub-typing of protein families will be a powerful combination for a broader coverage in proteomics. (C) 2003 Elsevier Ltd. All rights reserved.

A reference architecture for instructional educational software

Our extensive research has indicated that high-school teachers are reluctant to make use of existing instructional educational software (Pollard, 2005). Even software developed in a partnership between a teacher and a software engineer is unlikely to be adopted by teachers outside the partnership (Pollard, 2005). In this paper we address these issues directly by adopting a reusable architectural design for instructional educational software which allows easy customisation of software to meet the specific needs of individual teachers. By doing this we will facilitate more teachers regularly using instructional technology within their classrooms. Our domain-specific software architecture, Interface-Activities-Model, was designed specifically to facilitate individual customisation by redefining and restructuring what constitutes an object so that they can be readily reused or extended as required. The key to this architecture is the way in which the software is broken into small generic encapsulated components with minimal domain specific behaviour. The domain specific behaviour is decoupled from the interface and encapsulated in objects which relate to the instructional material through tasks and activities. The domain model is also broken into two distinct models - Application State Model and Domainspecific Data Model. This decoupling and distribution of control gives the software designer enormous flexibility in modifying components without affecting other sections of the design. This paper sets the context of this architecture, describes it in detail, and applies it to an actual application developed to teach high-school mathematical concepts.