title: Computational vaccinology: quantitative approaches.
abstract: The immune system is hierarchical and has many levels, exhibiting much emergent behaviour. However, at its heart are molecular recognition events that are indistinguishable from other types of biomacromolecular interaction. These can be addressed well by quantitative experimental and theoretical biophysical techniques, and particularly by methods from drug design. We review here our approach to computational immunovaccinology. In particular, we describe the JenPep database and two new techniques for T cell epitope prediction. One is based on quantitative structure-activity relationships (a 3D-QSAR method based on CoMSIA and another 2D method based on the Free-Wilson approach) and the other on atomistic molecular dynamic simulations using high performance computing. JenPep (http://www.jenner.ar.uk/ JenPep) is a relational database system supporting quantitative data on peptide binding to major histocompatibility complexes, TAP transporters, TCR-pMHC complexes, and an annotated list of B cell and T cell epitopes. Our 2D-QSAR method factors the contribution to peptide binding from individual amino acids as well as 1-2 and 1-3 residue interactions. In the 3D-QSAR approach, the influence of five physicochemical properties (volume, electrostatic potential, hydrophobicity, hydrogen-bond donor and acceptor abilities) on peptide affinity were considered. Both methods are exemplified through their application to the well-studied problem of peptide binding to the human class I MHC molecule HLA-A*0201.
authors.affiliation: Edward Jenner Institute for Vaccine Research, High Street, Compton, Berkshire, RG0 7NN, UK.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
authors.forename: Helen
authors.initials: H
authors.lastname: McSparron
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blythe
authors.forename: Christianna
authors.initials: C
authors.lastname: Zygouri
authors.forename: Debra
authors.initials: D
authors.lastname: Taylor
authors.forename: Pingping
authors.initials: P
authors.lastname: Guan
authors.forename: Shouzhan
authors.initials: S
authors.lastname: Wan
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coveney
authors.forename: Valerie
authors.initials: V
authors.lastname: Walshe
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Irini A
authors.initials: IA
authors.lastname: Doytchinova
mesh_terms: D000486:Allergy and Immunology / Q000706:statistics & numerical data; D019295:Computational Biology; D003198:Computer Simulation; D016208:Databases, Factual; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology; D013816:Thermodynamics; D014612:Vaccines
chemical_list: D000939:Epitopes; D014612:Vaccines