embrapaInterface region (in red) of the complex between the enzyme trypsin (blue) and an inhibitor (yellow), a useful formation for creating drugsembrapa
Revealing the complex structure of proteins is an essential task, both in the study of biological processes and in the pharmaceutical industry, and, in a more specific way, in the analysis of the post DNA sequencing results of any genome. To get to know and to interpret better the complexity of these molecules, many of the researchers from the area are now using a set of software developed by the Structural Bioinformatics Nucleus (NBI in the Portuguese acronym) of Embrapa Information Technology, from Campinas, one of the units of the Brazilian Agricultural Research Corporation (Embrapa). The new set of tools, called Gold Sting Suite (sequence to and within graphics-GSS), does a three dimensional analysis of the proteins that help the researchers to understand the whole ingenious functioning of molecules, including aspects like the formation of substances that are candidates for being the main components in the preparation of new drugs and agrochemicals.
The product is available on the Protein Data Bank (PDB) of the San Diego Supercomputer Center (SDSC), the largest databank of protein structures in the world, at the University of San Diego and Columbia University, both in the United States. It is also available at public laboratories in Europe, Asia and Latin America, as well as at the laboratories of Embrapa in Campinas and in Brasilia”, says researcher Goran Neshich, the leader of the NBI. Putting together all the known information about the structures of proteins and the level of detailing in one and the same application favor the world-wide acceptance of Gold Sting.
The set of programs arose from the need to integrate the tools for analyzing these structures, which previously required the use of several items of software for molecular analyses. Totally based on biological studies available on public databases, Embrapa’s system is different from the others that aim at this kind of research, for making possible a detailed collection of information about the sequence and structure of proteins, the nature of the atomic contacts between the amino acids, and information about the cavities and surfaces of the proteins and its connections as well. According to Goran, between 2,000 and 5,000 accesses a day are made to the application a day by the Internet.
With the software and the data bank, the researchers can analyze, for example, the functioning of the specific activities of each amino acid in the proteins. This analysis, with all the parameters attributed to them, permits the application of the knowledge acquired in systems that need experimental data. In practice, this means that it is possible to increase or to decrease the activity of a protein, and even to eliminate actions that are harmful to the organism, such as, for example, irritation to the skin or any other side effect from the cocktail of proteases (components of the medicines) against the HIV virus.
Data and parameters
At the moment, a major part of the researches in molecular biology involves the structure of the proteins, because the researchers are trying to get to know their functions and how they can be modified. The most recent version of the software set works simultaneously as an interface for visualizing all the information shown by the system and as a database of the characteristics of the structures of the proteins. “The NBI is the only laboratory in the world-wide ambit to offer products of this kind. There are 125 different parameters that describe each amino acid inside a protein structure”, says the researcher.
The research work at the NBI has received over R$ 2.8 million in investments, including the participation of FAPESP, of the Financier of Studies and Projects (Finep) and of the National Council for Scientific and Technological Development (CNPq). The researches at the laboratory in Campinas involve protein structures from animals and from plants, and they represent a potential in the world market estimated by an American consultancy at US$ 3 million. “We did not market the software, because it is included in the exchange of information between international public entities. The software is public, because the data used is also public”, he clarifies.
Since 1998, over 12 million access have now been made to the applications of Gold Sting and of its earlier versions. The companies from the pharmaceutical sector are also using the product, but only for training and assessing the potentialities of the software itself and of the data bank. “Although they have great interest in the research, the companies do not do them by public channels, so as not to run the risk of having their private studies known publicly. That is why the best option for them would be to acquire the software, to work on their own computers, outside the public network”, he concludes.
New versions
With latest generation, the data collected by the NBI is processed, calculated and stored, before being made available. To do so, the nucleus has six permanent researchers in a multidisciplinary group made up of a mathematician, two electrical engineers with a specialization in software, a physicist specialized in protein crystallography, a bioinformatician, and a biophysicist. They have the prospect of new updatings of the software in 2005, with the launch of the Diamond Sting version, and, in 2006, with Star Sting. At this point, the NBI should finalize the creation of software interfaces, aimed at the management of information, analyses, and grouping of data.
Although, in comparative terms, they are smaller than those of the major world bioinformatics centers, Brazilian researches in this area have grown considerably, so much so that the country has been chosen to host, in 2006, the 14th International Conference on Intelligent Systems in Molecular Biology, organized by the International Society for Computational Biology and which for the first time will be leaving the Europe United States axis. Goran is betting on the impact that the discussion with international researchers will bring to the Brazilian researches (further information on the website http://www.iscb.org/ismb_2006). To do so, the creation of the Brazilian Society of Bioinformatics and Computational Biology is being arranged, to gather together researchers at the national level. The intention is also to strengthen Gold Sting by 2006, making it possible for the product to be used more and more.
The Project
Creation of a center for research and supplying services in bioinformatics (CB) (nº 01/08895-0); Modality Regular Line of Research Grants; Coordinator Goran Neshich – Embrapa Information Technology; Investment R$ 185,731.72 and US$ 285,741.10 (FAPESP Project) and R$ 488,669.03 (CNPq) and R$ 762,884.16 (Finep)
