Experimental design computation, interactions

Melani F, Gratteri P, Adamo M, Bonaccini C. Field interaction and geometrical overlap (FIGO) a new simplex/experimental design-based computational procedure for superposing small ligand molecules. J Med Chem 2003 46 1359-71. 

The theoretical prediction of free binding energy differences, and the understanding of the physical foundations of affinity and specificity of complex interaction, prior to experimental design are crucial in computational biochemistry.48,64 To apply... 

Atom-Atom Interactions. - The methods applied, usually to interactions in the inert gases, are a natural extension of diatomic molecule calculations. From the interaction potentials observable quantities, especially the virial coefficients can be calculated. Maroulis et al.31 have applied the ab initio finite field method to calculate the interaction polarizability of two xenon atoms. A sequence of new basis sets for Xe, especially designed for interaction studies have been employed. It has been verified that values obtained from a standard DFT method are qualitatively correct in describing the interaction polarizability curves. Haskopoulos et al.32 have applied similar methods to calculate the interaction polarizability of the Kr-Xe pair. The second virial coefficients of neon gas have been computed by Hattig et al.,33 using an accurate CCSD(T) potential for the Ne-Ne van der Waals potential and interaction-induced electric dipole polarizabilities and hyperpolarizabilities also obtained by CCSD calculations. The refractivity, electric-field induced SHG coefficients and the virial coefficients were evaluated. The authors claim that the results are expected to be more reliable than current experimental data. 

This means that three- and four-factor interaction effects were assumed to be small compared to the experimental error. The model contains 11 parameters and the experimental design contains 16 runs. The excluded higher order interaction effects allow an estimate of the residual sum of squares, SSE, which will give an estimate of the experimental error variance, s with 16 - 11 = 5 degrees of freedom. This estimate can then be used to compute confidence limits for the estimated model parameters so that their significance can be evaluated. 

In addition to the methods described above, those useful for quantifying metal ion mixture bioactivities were also discussed. The general models described in Chapter 1 are implanented with specific computer code to illustrate the two potential approaches. The first is based on similar joint action, assumes identical slopes for similar acting metal ions, and measures deviations from identical slopes in order to quantify departure from the assumption of similar action. This involves only probit models for the individual metal ions alone. The second approach, which is based on joint independent action, requires an experimental design in which different concentrations of each metal ion are in mixture with those of the second metal ion. An interaction coefficient, p, quantifies deviations from the assumption of independent action. 

---