title: Peptide recognition by the T cell receptor: comparison of binding free energies from thermodynamic integration, Poisson-Boltzmann and linear interaction energy approximations.
abstract: The binding to the T cell receptor of wild-type and variant HTLV-1 Tax peptide complexed to the major histocompatibility complex has been investigated by means of molecular dynamics simulations. The binding free energy difference is calculated using the molecular mechanics Poisson-Boltzmann surface area and linear interaction energy methods. These methods extract useful information on the binding energetics from simulations of the physical states of the ligands, which are more computationally expedient than the commonly used thermodynamic integration method. The successful reproduction of the relative binding free energies shows that these methods can be useful for free energy calculations and the rational design of drugs and vaccines.
authors.affiliation: Centre for Computational Science, Department of Chemistry, University College London, UK.
authors.forename: Shunzhou
authors.initials: S
authors.lastname: Wan
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coveney
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D004735:Energy Transfer; D016356:Gene Products, tax / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D016014:Linear Models; D008432:Mathematical Computing; D008956:Models, Chemical; D018448:Models, Immunological; D008958:Models, Molecular; D015233:Models, Statistical; D016012:Poisson Distribution; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology*; D018511:Systems Integration; D013816:Thermodynamics
chemical_list: D016356:Gene Products, tax; D011948:Receptors, Antigen, T-Cell