Improvement of charge-transfer indices for multifunctional amino acids: Application to lysozyme†

Abstract

Valence topological Charge-Transfer (CT) indices are applied to the calculation of pH at the isoelectric point (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 superimposition of the corresponding Gk –Jk and 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, the because of either the role of the additional p orbitals provided by heteroatom or the role of steric factors in π-electron conjugation. The use of CT/valence CT indices {Gk , Jk , } gives limited results for modelling amino acid pI. The inclusion of the number of acidic/basic groups improves the models. The effect is specially noticeable for amino acids with more than two functional groups. The fitting line for 21 amino acids is used to estimate lysozyme pI replacing (1 + Δn/n T) with (M + Δn)/n T. The results for lysozyme fragments can estimate the pI of the whole protein with 1–13% error. †Presented at the 13th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.