Residue interaction database: proposição de mutações sítio dirigidas com base em interações observadas em proteínas de estrutura tridimensional conhecida

Abstract

In this work we describe an algorithm which is used to predict amino acid residue pairs in target proteins (with known 3D structure) that could be replaced by a different amino acid residue pair in order to introduce a new/different interaction between residues. This might result in an in silico mutant with stereochemistry possibilities to exist in vitro with increased thermo and conformational stability. To address this, we have created a PDB-based database composed of pairs of interacting amino acid residues observed in proteins with known structure. The mutations are proposed in a way to maintain the target protein's fold (and function) as, basically, the main chain conformation of mutated residues are supposed to be conserved. In this work we also present the main aspects of this database, the way to find the mutation points and some results. A complete search in a target protein structure was performed to identify each residue pair that could be mutated using some of the pairs in the database. We intend to use this procedure to verify a number of possible mutations in different enzymes with potential application in bioremediation processes, where aggressive environmental conditions are expected. We present RID (Residue Interaction Database), a novel database and algorithm to propose a residue pair mutation in a protein aiming to increase its stability focusing in the conformation maintainability. We describe the details of the algorithm do generate the database of interacting amino acid residues and the method to optimize the database for quick searches. Compared to other methods, RID increases the alternatives to propose mutation because of the variety of the interactions used to create the database and that will contribute to increase the protein stability. The tool is available at: http://www.bioest.icb.ufmg.br/RID.