PROTEINS STUDIED IN ORDER TO GENERATE NEW MEDICAMENTS

FONDECYT PROJECT EXPLORES THE BEHAVIOR OF BIOMOLECULES AND THEIR INTERACTION WITH OTHER ELEMENTS GENERATED AT THE CELLULAR LEVEL, WHICH WOULD ENABLE THEM TO FIGHT DISEASE.



February 29, 2016

Professor Julio Caballero’s scientific project is in its final phase, in the School of Civil Engineering in Bioinformatics, of the Department of Engineering. The academic carries out a study in the area of basic science and seeks to learn how to operate some types of biomolecules that are in our body.

The academic stressed the importance of studies of this type, indispensable for the subsequent development of therapies for various health problems that afflict the population.

“In the last few decades it has been invested heavily worldwide in the study of kinase proteins at the molecular level —that is what I investigate— as it is known that overexpression of many of these proteins are associated to some varieties of cancer”, he explained.

And it is in this area where he developed his Regular Fondecyt project called “Understanding the Structural Basis of the Interactions between the Kinase Protein Dependent on Cyclic AMP (PKA) and Its Substrates: Development of Predictive Molecular Models and Assessment in the Study of the Interactions between PKA and the Potassium Channel AKT2”. The work lasted 3 years, finishing during the first half of this year.

Caballero said that the studies that have been conducted on the topic have revealed various aspects about the form and mechanisms of these proteins. This has led specialists to design at least eight drugs used in therapy of cancer.

“This figure is an improvement, but it is not enough for the quantity of medical conditions involving the proteins called kinases (PKs),” said the scientist of our University.

The dean of the Department of Engineering, Claudio Tenreiro, highlighted the scientific excellence developed by a group of academics in Bioinformatics, to which belongs Professor Caballero. “There are a number of areas of research in the Department where the critical mass is relevant, and Bioinformatics is one of the areas in which we have excelled with national and international presence”, he said.

Positive Results

During the project, theoretical calculations were done to reproduce the interaction between the PKA protein —that is one of the proteins of the kinases family (PKs) - and peptide substrates, specifically one named Kemptido, and others similar to it. For this we used two methods of calculation.

“We reproduced the experimental values of the interactions in these systems and we observed, at the molecular level, which are the chemical interactions responsible for the difference of affinity between the Kemptido and its mutants,” explained Caballero.

In addition, we studied computationally the structure of another PKA-type PK protein taken from a plant, and analyzed what happens in a potassium channel. We distinguished differences between the same protein generated in man and in the plant. For this year the project includes the study of the protein PKA kinase with a peptide containing an unnatural amino acid.

“Working with an unnatural amino acid is complicated, because it must generate parameters for this biological molecule, i.e., an additional programming work was required that allowed for the incorporation of the new molecule within the protocol of the work programs”, said the academic.

“We propose a simple methodology to address the calculation of the interaction energy between PKA and its peptide substrates, which in addition allows us to understand in detail the molecular interactions that guide this process. Our methodology requires a low resources expenditure since it is a computational approach,” said Julio Caballero.

Foreign Researchers

During the development of the project seven academics visited the University, coming from the Universities of Lund, in Sweden; Federal de São Carlos, Sao Paulo, Brazil; Havana, Cuba; and the Instituto Pasteur of Montevideo, Uruguay. The scientists, in addition to working in several areas with professor Caballero, carried out dissemination activities of their research with undergraduate students of Engineering in Bioinformatics, and also students of a postgraduate program of our Corporation.

Caballero pointed out that another positive aspect of the project was that during its execution, ten scientific articles in international journals of high impact were generated.

In addition, there were resources to support doctoral and undergraduate theses in the area. It was also possible to purchase several computers to allow the development of complex calculations. This equipment is used on a permanent basis in the Center for Bioinformatics and Molecular Simulation, Department of Engineering.

A kinase protein is an enzyme capable of modifying other intracellular proteins through phosphorylation, activating them, or turning them off. They have a fundamental place in the response to a chemical signal that reaches the cell. Due to their relationship in the development of certain diseases, they are studied for certain drugs to carry out their action.



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