Modelización molecular de los receptores de adenosina y sus ligandos en el marco de diseño de fármacos asistido por ordenador

Abstract

The goal of the present thesis is to gain knowledge about the biochemistry and pharmacology of adenosine receptors, as well as to understand structure-activity relationships for the existing ligands for this receptors. In order to achieve this goal, we have used several techniques and methodologies from the computer-aided drug design field. Results presented in this work include: · The development of an original strategy of selection of a maximum diversity sample that adequately covers the original molecular diversity contained in a compound database · The building of the transmembrane region of a human A1 adenosine receptor model. In such a model, an agonists binding site has been located and characterized, showing agreement with experimental data. · The resulting ligand-receptor complexes have been studied with computational approaches for the prediction of ligand-binding free energies. A nice correlation with experimental results was observed