The City of Barcelona Award 1998 for Scientific Research has gone to Dr. Francesc Xavier Avilés for his work in protein engineering and research in experimental and computational molecular biology in particular, which has allowed him to identify several agents and their inhibitors. In fact, Dr. Avilés considers the award as the achievement of a whole team of researchers at the Institute of Fundamental Biology (IBF) in the Department of Biochemistry at the Free University of Barcelona (UAB). This research will likely have a substantial impact on biomedical and agronomic applications.
The Institute of Fundamental Biology was established in 1970 at UAB with the aim to promote and carry out multi-disciplinary research in the fields of biomedicine and biotechnology. The Institute offers services to the scientific community by providing access to data and analyses from its genetic database and by sharing biomolecular predictions and simulations. The protein engineering group is formed out of four laboratories, three at IBF and one in the Department of Biochemistry, which are all coordinated by Dr. Avilés. The team consists of 30 scientists, of which 5 to 8 are directly involved in bio-computation.
The research is specifically concentrated on the enzymes, forming part of the proteins, and their inhibitors. The team investigates how different molecules are involved in a suite of biological phenomena which play an important role in a vast range of pathologies, such as inflammations, and viral or cancerous proliferation. The interconnections enable the scientists in collaboration with the pharmaceutical industry, to discover molecular variants that are suitable to study crucial factors relating to health care and new drugs design. Next to this, the agents' inhibitors can also be used to protect the agricultural plants against harmful insects.
To this purpose, molecules are redesigned within the IBF engineering group. Computational methodologies are applied to identify the new molecules that are created with experimental techniques. The research team stands on the bridge between computational and experimental applications and makes use of different types of computational methods. Some of them require a modest amount of power like graphical methods for topological analysis or statistics. For others like semi-empirical calculations or molecular dynamics, very vast resources are needed.
The IBF scientists apply the computational methods in particular to facilitate a fast identification and engineering of the proteins. One of the objectives is to generate variants of redesigned molecules that can be either more or less active, or which are easier to produce. The molecules are redesigned in order to penetrate cellular membranes, to operate without any toxic effects, and so on. Therefore, the scientists must recognize the exact structure and discover whether the form, functions and mecanisms of the redesigned molecules are similar to their natural counterparts.
In this complex research, computational methodologies are extremely helpful for sequence comparison, topologies and conformations, modelling, dynamic simulation, and drugs analysis. The research team is equally involved in the computational prediction of the structures and functions, displayed in newly discovered proteins in several large projects of genome analysis. Though very often, computational methods applied to large proteins at present are not yet sufficiently accurate to generate results similar to quantitative experimental testing, they are more than useful to gain insight into many natural systems which are inaccessible for experimental research.
The IBF research team intends to develop innovative methods of analysis and protein engineering in order to apply them to practical cases afterwards. The group currently can benefit from the large experience it has been building up in molecular research to create models for new computational methods. This type of combined research is very much used and can be of great assistance to the comprehensive structural genome projects which are in process. We kindly refer to the interview with Dr. Avilés in the June 1999 issue of the Catalonian supercomputer magazine Teraflop which served as the news source for the VMW article.