https://doi.org/10.1140/epjd/e2008-00009-3
A rational method for probing macromolecules dissociation: the antibody-hapten system
Johann Wolfgang Goethe University, Frankfurt Institute for Advanced Studies, Ruth-Moufang-Strasse 1, 60438 Frankfurt am Main, Germany
Corresponding author: a solovyov@fias.uni-frankfurt.de
Received:
3
March
2007
Revised:
14
September
2007
Published online:
23
January
2008
The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the dissociation paths of the system by probing only a relevant set of generalized coordinates. The complex problem was reduced to a low-dimensional scanning along a selected distance between the protein and the ligand. Orientational coordinates of the escaping fragment (the ligand) were also assessed in order to further characterise the unbinding. Solvent effects were accounted for by means of the Poisson–Boltzmann continuum model. The corresponding dissociation time was derived from the calculated barrier height, in compliance with the experimentally reported Arrhenius-like behaviour. The computed results are in good agreement with the available experimental data.
PACS: 82.20.Kh – Potential energy surfaces for chemical reactions / 82.20.Pm – Rate constants, reaction cross sections, and activation energies / 87.14.Ee – Proteins / 87.15.-v – Biomolecules: structure and physical properties
© EDP Sciences, Società Italiana di Fisica, Springer-Verlag, 2008
