Structures Databases Personal Computer

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

Molecular mechanics is an interpolative method. It thus follows that the strain energy and the stmcture of a very strained species may not be reliably computed based on a parameterization scheme fitted with a set of experimental data obtained from unstrained molecules, as this amounts to extrapolation. Therefore, in order to obtain a generally reliable force field, extreme cases must be included in the fitting procedure of the force field. The speed with which structure optimizations are produced (seconds of CPU time on a simple personal computer for molecules with a few hundred atoms) does not place any restriction on the size of a database for the... 

An important factor in the progress of bioinformatics has been the constant increase in computer speed and memory capacity of desktop computers and the increasing sophistication of data processing techniques. The computation power of common personal computers has increased within 12 years approximately 100-fold in processor speed, 250-fold in RAM memory space and 500-fold or more in hard disk space, while the price has nearly halved. This enables acquisition, transformation, visuahsation and interpretation of large amounts of data at a fraction of the cost compared to 12 years ago. Presently, bioanalytical databases are also growing quickly in size and many databases are directly accessible via the Internet One of the first chemical databases to be placed on the Internet was the Brookha-ven protein data bank, which contains very valuable three-dimensional structural data of proteins. The primary resource for proteomics is the ExPASy (Expert Protein Analysis System) database, which is dedicated to the analysis of protein sequences and structures and contains a rapidly growing index of 2D-gel electrophoresis maps. Some primary biomolecular database resources compiled from spectroscopic data are given in Tab. 14.1. 

Figure 1 shows a schema for an ideal distributed chemical information system. Several authors in this book refer to the need for standard interfaces. Ultimately, the personal computer will provide the graphics interface not only to personal computer databases but also to company databases running on the company mainframe, and possibly also through the same network to public hosts, so that the chemist using a personal workstation will be able to create queries which can be addressed to local files, company files and public files. Soon, chemical databases will be available on Compact Disk Read Only Memory (CD-ROM) searchable by both substructure and text. These too fit into the scheme of Figure 1. Databases such as infra-red spectra libraries will have structure-searchable components either on the personal computer or on the laboratory instrument and will also be used through the same graphical interface.

The earliest chemical databases which became available on PC s were not structure-based. In the UK one of the first chemical databases distributed on personal computers was the hazards database CHEMDATA which was developed at the Chemical Emergency Centre at Harwell. This was a database created primarily for the emergency services to help deal with chemical emergencies. Initially, the database was offered as an online service, but obviously the need to keep this service operational 24 hours a day, 7 days a week, put tremendous strains on the operators of the service and as soon as the first microcomputers were introduced, the Chemical Emergency Centre recognised their potential for distributing the data in another form. 

The algorithm incorporates recently determined thermodynamic parameters for the free energies of internal loops of 2 by 1 and 2 by 2 nucleotides. New free energy bonuses for tetraloops and triloops have been developed by consideration of the database of phylogenetically determined structures. Finally, new rules for coaxial stacking have been applied. This new version will be available in FORTRAN for Unix machines and a C++ version is now available for use on Personal Computers with Windows 95 or Windows NT. The program was used to explore structures predicted to have a free energy near the minimum. 

In spectra-structure correlation problems, the spectral representations, be it for IR, for mass, or for any other spectroscopy, are usually input as sets of equidistant intensities with significantly high resolution. Such inputs require hundreds if not thousands of units on input. Additionally, the intensities of spectra are given as real values and mostly large data bases of spectra have to be taken into account if reliable predictions are to be expected (see Spectroscopic Databases). Therefore, spectra-structure correlation problems have to be implemented on larger and faster work-stations (or mainframes) rather than on personal computers. ... 

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