Unravelling the orientation and dynamics of membrane peptides
- Autores: Santiago Esteban Martín
- Directores de la Tesis: Jesús Salgado Benito (dir. tes.)
- Lectura: En la Universitat de València ( España ) en 2009
- Idioma: español
- Tribunal Calificador de la Tesis: Modesto Orozco López (presid.), Iñaki Tuñón García de Vicuña (secret.), Siewert-Jan Marrink (voc.), Xavier Daura i Ribera (voc.), Stephan L. Grage (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
During the last 10 years a number of spectroscopic techniques have developed and matured enough to allow the precise determination of the orientation of membrane peptides based on experimental measures. Because most of the available experimental orientational information is based on static models, this Thesis aims to expand this view and focus on the dynamics of the peptide-membrane systems. Of special interest are the model transmembrane peptides from the WALP/WLP and KALP/KLP series, designed to understand membrane peptide interactions in detail. Despite their apparent simplicity, these systems have become controversial as their tilt in the membrane, determined from 2H NMR data, has been reported to be smaller than expected and barely reacting to mismatch, which contrast to that observed for a number of natural peptides.
This Thesis is organized as follows: Chapter 7 addresses the origin of discrepancies encountered between computational methods and 2H-NMR spectroscopy for the determination of peptide orientation. This is studied by molecular dynamics simulations. Chapters 8 and 9 are a systematic analysis of the effect of whole-body peptide motions on 2H-splittings and 2D PISA wheels. In Chapter 10 the thermodynamically available positional and orientational states of (rigid) peptides in implicit membranes are explored based on the free energy of partitioning aminoacid residues into the interface or the hydrophobic parts of bilayers. In Chapter 11 we investigate the capability of a random distribution of lipids and a peptide to self-organized in water into a lipid bilayer. We show that this method allows obtaining non-biased membrane-protein systems for the study of preferred membrane-peptide binding modes at atomic detail.
