Correction of Charge-Transfer Indices for Multifunctional Amino Acids: Application to Lysozyme

Valence topological charge-transfer (CT) indices are applied to the calculation of pH at the pI isoelectric point. The combination of CT indices allows the estimation of pI. The model is generalized for molecules with heteroatoms. The ability of the indices for the description of molecular charge distribution is established by comparing them with the pI of 21 amino acids. Linear correlation models are obtained. The CT indices improve multivariable regression equations for pI. The variance decreases by 95%. No superposition of the corresponding G_k–J_k and G_k^V–J_k^V pairs is observed in most fits, which diminishes the risk of collinearity. The inclusion of heteroatoms in π-electron system is beneficial for the description of pI, owing to either the role of the additional p orbitals provided by heteroatom or role of steric factors in π-electron conjugation. The use of only CT and valence CT indices {G_k,J_k,G_k^V,J_k^V} gives limited results for modelling pI of amino acids. Furthermore, the inclusion of the numbers of acidic and basic groups improves all models. The effect is specially noticeable for amino acids with more than two functional groups. The fitting line obtained for the 21 amino acids can be used to estimate the isoelectric point of lysozyme and its fragments, by only replacing (1+Δn/n_T) with (M+Δn)/n_T. For lysozyme, the results of smaller fragments can estimate that of the whole protein with 1–13% errors.