Molecular Modelling studies of Ohr from Xylella fastidiosa in its "open" conformation and selection of inhibitors by virtual screening procedures

• Grant number: 10/07660-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2010
• End date: May 31, 2011
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Antonia Tavares Do Amaral
• Grantee: Maria Christina Camasmie Peters
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Abstract: Xylella fastidiosa is a bacterial pathogen causing various diseases in plants such as citrus variegated chlorosis (CVC). In the xylem of the plants, this bacterium blocks the passage of the sap, leaving the fruits hard and small, ffecting their trade. The Ohr (Organic hydroperoxide Resistance) is a unique bacterial protein that promotes resistance against oxidative stress promoted by the plant in response to the pathogen. The structure of Ohr from X. fastidiosa was solved by X-ray crystallography and can be used as a valid target for the search for new pesticides against CVC. The rational design of compounds based on the structure of the biological target is a modern strategy for development of bioactive compounds. It is based on information extracted from the structure of the macromolecule target for selection of potent ligands and against specific targets. Based on preliminary studies carried out in the group [Seixas et al., 2008] in this project we intend to apply modern SBDD strategies for the selection of specific inhibitors for Ohr of X. fastidiosa. In this project we intend to develop a homology model of the Ohr of X. fastidiosa in its "open." conformation. This model will be validated by molecular dynamics and will be used to build a virtual screening model (VS) based on the structure of this protein. The VS model is built, initially, from docking and pharmacophore filters [Malvezzi et al, 2008, Malvezzi et al, 2009], that will be used to search ligands from Ohr of X. fastidiosa in the ZINC database. The selected compounds will be tested by enzymatic assays to experimentally validate the model.