Protein-protein interaction investigated by steered molecular dynamics: the TCR-pMHC complex.

Détails

ID Serval
serval:BIB_1B86AF5D4CDD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Protein-protein interaction investigated by steered molecular dynamics: the TCR-pMHC complex.
Périodique
Biophysical journal
Auteur(s)
Cuendet M.A., Michielin O.
ISSN
1542-0086[electronic]
Statut éditorial
Publié
Date de publication
2008
Volume
95
Numéro
8
Pages
3575-3590
Langue
anglais
Résumé
We present a novel steered molecular dynamics scheme to induce the dissociation of large protein-protein complexes. We apply this scheme to study the interaction of a T cell receptor (TCR) with a major histocompatibility complex (MHC) presenting a peptide (p). Two TCR-pMHC complexes are considered, which only differ by the mutation of a single amino acid on the peptide; one is a strong agonist that produces T cell activation in vivo, while the other is an antagonist. We investigate the interaction mechanism from a large number of unbinding trajectories by analyzing van der Waals and electrostatic interactions and by computing energy changes in proteins and solvent. In addition, dissociation potentials of mean force are calculated with the Jarzynski identity, using an averaging method developed for our steering scheme. We analyze the convergence of the Jarzynski exponential average, which is hampered by the large amount of dissipative work involved and the complexity of the system. The resulting dissociation free energies largely underestimate experimental values, but the simulations are able to clearly differentiate between wild-type and mutated TCR-pMHC and give insights into the dissociation mechanism.
Mots-clé
Algorithms, Amino Acid Sequence, Histocompatibility Antigens/chemistry, Histocompatibility Antigens/metabolism, Humans, Models, Molecular, Molecular Sequence Data, Oligopeptides/chemistry, Oligopeptides/metabolism, Protein Binding, Protein Interaction Mapping/methods, Protein Structure, Secondary, Receptors, Antigen, T-Cell/chemistry, Receptors, Antigen, T-Cell/metabolism, Thermodynamics
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/03/2009 13:51
Dernière modification de la notice
20/08/2019 12:52
Données d'usage