Tesis doctoral de Francesc Corcho Sánchez
The present work focuses on the exploration of the conformational space of biological active peptides in different conditions with the aim of characterizing their conformational profile. Different techniques have been used within the molecular mechanics framework. determining the bioactive conformation is a requirement for the design of peptidomimetics in computer-aided drug design. In chapter 2, the conformational profile of 4-residue long farnesyltransferase inhibitors is studied by means of the iterative simulated annealing procedure yielding as a result the bioactive conformation. This bioactive conformation can be simplified by the moieties that are known to interact with the receptor and the relative distances between these moieties, and this schematic entity is termed pharmacophore. the pharmacophore can be used to screen three-dimensional databases of molecules for the search of peptidomimetics. The compounds obtained in the search can be subsequently tested for activity and a new group of lead compounds can be thus identified. In chapter 3 an example of this procedure is described with the aim of obtaining a new group of bradykinin antagonists based on hoe 140. The pharmacophore obtained was tested on a group of 5-residue long bradykinin analogs containing 1-amino-2-phenylclyclopropanecarboxylic acid, a conformationally restricted residue. recently, it has been reported several instances were the folding of peptides has been simulated by means of long molecular dynamics trajectories. A problem arises when the wealth of conformations obtained has to be classified in terms of their respective degree of folding. In chapter 4 a novel methodology is described for the classification and grouping of the peptide structures based on the presence of structural motifs and the similarities among them. this methodology can prove very useful as it is almost automated and it does not present any limitation regarding the size of the peptide
Datos académicos de la tesis doctoral «Computational studies on the structure and dynamics of bioactive peptides.«
- Título de la tesis: Computational studies on the structure and dynamics of bioactive peptides.
- Autor: Francesc Corcho Sánchez
- Universidad: Politécnica de catalunya
- Fecha de lectura de la tesis: 26/01/2004
Dirección y tribunal
- Director de la tesis
- Juan Jesús Perez Gonzalez
- Tribunal
- Presidente del tribunal: ernest Giralt lledo
- Jaime Rubio Martinez (vocal)
- Van der spoel david (vocal)
- patrik Bultinck (vocal)