Charybdotoxin (ChTX) is a 37-residue polypeptide that has been extensively used in site-directed mutagenesis experiments as a template to deduce models for the external pore appearance of K+ channels. The microscopic details of the ChTX-channel interaction, however, remain as a challenge for experimental and theoretical approaches. In this work, regional charge-transfer abilities, measured by chemical softness, s(r), are used as companion properties of the electrostatic potential, V(r), in the search for a qualitative structure-function relationship in the ChTX-K+ channel interaction. Both quantities were obtained with an ab initio methodology in massively parallel computers. In the analysis of s(r) and V(r), regions of the size of amino acids were considered because this is the appropriate scale to correlate with site-directed mutagenesis experiments. The correspondence between experimentally identified crucial amino acids sites and regional softnesses indicates that charge transfer to ChTX could be one of the main stabilization effects in the ChTX-channel complex. Also, it provides an explanation for the strong dependence of the dissociation constant of the complex on mutations of crucial amino acids. In addition, it is shown to be feasible to find structure-function relationships by combining local reactivity parameters and experimental data involving site directed mutagenesis.