Structural biology investigates the molecular basis of life in its healthy and diseased states. Initially through x-ray diffraction (Perutz et al., 1960; Kendrew et al., 1960;), later through NMR ( Wuethrich, 1986 ), and lately also through electron microscopy ( Nogales et al., 1998 ), ever more medically relevant and larger biomolecular structures have been discovered.
The blossoming field of genomics rivals structural biology with an outpouring of genomes. The vast amount of information available and the complexity of the information units, gene sequences and protein structures, have made computers indispensable tools in biomedical research to an extent which in 1991 was characterized as a paradigm shift by W. Gilbert ( Gilbert, 1991 ). Today about 200 different programs serve researchers well, in particular those coupled with web-based tools such as the Biology Workbench, PROPSEARCH ( Hobohm and Sander, 1995 ), and BLAST ( Altschul et al., 1990 ). Programs for structural biology have been mostly single-user oriented and not integrated with web-based tools. Here we suggest to develop a ``Biological Collaborative Research Environment'' (BioCoRE), an integrated, web-based, and tool-oriented computing and communication system for biomolecular modeling and simulation.
Structural biology, similar to its molecular biology parent, traditionally existed in small, independent laboratories. The need for expensive instrumentation (e.g. x-ray sources), the scale of tasks such as sequencing the human genome, the sharing of large data bases, the requirement of broad expertise and of cutting-edge technology have all led to many trans-mural groups ranging from collaborations between two laboratories to national consortia. Fortunately, this development coincides with the great performance increase of the US research network so that communication, data sharing, and joint use of instrumentation and computing facilities can be realized on the necessary scale ( Schooler, 1996 ; Kouzes et al., 1996 ; Shortliffe et al., 1996 ; Clutter, 1996 ; Finholt and Olson, 1997 ). The wide bandwidth network connects the structural biology community today to massively parallel powerful computers, ``pumping data back to their local site for immediate visualization'' ( UCAID, 1997 ). An adequate use of this resource for analysis and modeling of increasingly complex structures or for real time interactive modeling, requires a new type of web-based modeling which exploits distributed computing as well as a unification of graphics and molecular dynamics (MD) simulation.
Collaborative projects in structural biology demand new software tools which can be classified into four categories:
BioCoRE design supports four basic types of activities pertinent to most research projects: utilizing a wide range of computational tools, keeping records, communicating with collaborators, and writing articles and reports. This functionality will be implemented in four main interfaces of BioCoRE, called Workbench, Notebook, Conferences, and Documents (Fig. 1).
The Workbench interface of BioCoRE includes features for controlling molecular modeling, simulation, and bioinformatics tools with convenient and uniform access to collaboratory data. The Notebook interface furnishes the tools for logging, locating, and reviewing methodology, data, results, and annotations related to the ongoing projects. Scientists are able to discuss their research in real time or time-delayed sessions via the Conferences interface, which spawns software for teleconferencing and synchronized visualization of shared data at distant sites. The Documents interface of BioCoRE supplies collaborators with a convenient front end for preparing multi-author documents for publication.
BioCoRE is a general web-based collaboratory tool that leads to accelerated development and dissemination of basic biomedical knowledge. This network-centered meta-application improves the collaboration between biomedical researchers located at either the same institution or at geographically distant places. It facilitates the transparent use of and communication between existing programs, tools, and databases. BioCoRE allows researchers to share information and resources. Scientists interact in both synchronous and asynchronous fashion with each other or with the modeling tools via a common infrastructure. BioCoRE enables scientists to initiate new collaborations through its communication interface and reduces the need for travel between the participating research groups.