title: Exploring the properties of small molecule protein binding via molecular simulations: the TRSH-p53 core domain complex.
abstract: Molecular dynamics simulations have been performed to investigate the binding of tris(hydroxymethyl)-aminomethane to the surface of the core domain of the mouse cellular tumor antigen p53 employing the GROMOS  and 53A6 force field parameter sets. A close investigation of the crystal structure reported by Ho et al. revealed that the protonated form is bound to the protein, i.e. a tris(hydroxymethyl)-methylammonium ion (TRSH). Molecular Dynamics (MD) simulations indicate that the p53 protein gains stability upon binding the ligand. In addition to MD simulations of the p53 protein with and without the TRSH compound, thermodynamic integration was utilised to estimate the free enthalpy of binding of the TRSH-p53 complex, which was estimated to be -49 and -54 kJ mol(-1) utilising the  and 53A6 force fields, respectively.
authors: Theoretical Chemistry Division, Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria. t.hofer@uibk.ac.at
authors: Thomas S
authors: TS
authors: Hofer
authors: Wilfred F
authors: WF
authors: van Gunsteren
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D008744:Methylamines / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055550:Protein Stability; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008744:Methylamines; D016159:Tumor Suppressor Protein p53; C027451:methylamine