Tesis doctoral de Arnau Cordomi Montoya
Seven transmembrane g protein coupled receptors (gpcr) constitute the largest family of integral membrane proteins in eukaryotes, with more than 1000 members and encoding more than 2 % of the human genome. These proteins play a key role in the transmission and transduction of cellular signals responding to hormones and neurotransmitters and regulating basic biological processes. Their natural abundance together with their localization in the cell membrane makes them suitable targets for therapeutic intervention. Therefore, gpcr are proteins with enormous pharmacologic interest, representing the targets of about 50 % of the currently marketed drugs. the current limitations in the experimental techniques necessary for microscopic studies of the membrane as well as membrane proteins emerged the use of computational methods and specifically molecular dynamics simulations. The lead motif of this thesis is the study of gpcr by means of this technique, with the ultimate goal of developing a methodology that can be generalized to the study of most gpcr as well as other membrane proteins. Since the bovine rhodopsin is the only protein of the gpcr family with a known three-dimensional structure at an atomic level, most of the effort is centered in the study of this receptor as a model of gpcr. the work presented in this thesis addresses the study of both the effect of the simulation conditions and system choices in getting optimal results, as well as specific structural and dynamical aspects with biochemical interest. Within the first group, the bovine rhodopsin has been studied using different treatments of long-range electrostatic interactions and sampling conditions, as well as embedded in various one-component lipid bilayers. The binding of ions to lipid bilayers without proteins has also been investigated. Regarding the second group, the binding site of retinal and its implications in the isomerization, the alteration a group of residues forming an electrostatic lock b
Datos académicos de la tesis doctoral «Molecular dynamics simulations of seven-transmembrane receptors«
- Título de la tesis: Molecular dynamics simulations of seven-transmembrane receptors
- Autor: Arnau Cordomi Montoya
- Universidad: Politécnica de catalunya
- Fecha de lectura de la tesis: 11/03/2008
Dirección y tribunal
- Director de la tesis
- Juan Jesús Perez Gonzalez
- Tribunal
- Presidente del tribunal: olle Edholm
- serge Crouzy (vocal)
- leonardo Pardo carrasco (vocal)
- Marta Filizola (vocal)