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The charges of the two cobalt ions present in the active site and of the side-chains involved in their binding were computed using ab-initio methods.
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The prediction of TF binding was computed using the TRANSFAC (Release 2010.2) [ 45] human binding motif position weight matrices (PWMs) (altogether 618 models) with the pseudocount 0.005.
Reciprocal serum dilutions corresponding to 50% maximal binding (EC50) were computed using the GraphPad Prism 4. Blood lymphocytes were purified on a density gradient.
The binding windows were computed using a genetic programming algorithm [ 29].
Combined quantum mechanical and molecular mechanical (QM/MM) calculations were used for the p Ka calculation, while the binding free energies were computed using pure molecular mechanical potentials.
Reciprocal plasma dilutions corresponding to 50% maximal binding (i.e EC50) were computed using the Prism software (v. 4.00; GraphPad Software Inc).
The binding affinities to the σ1 receptor were computed using Eq. 4: Delta G^{exp } = - RT ln K_{i} (4 where R is the ideal gas constant and T is the absolute temperature.
The binding free energies of podophyllotoxin-based inhibitors of tubulin were computed using a linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model.
Trend analyses were computed using joinpoint analysis.
Comparative statistics were computed using SPSS 17.0.
All statistics were computed using R [49].
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