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 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 pi-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 pi-electron conjugation. The use of CT/valence CT indices {G(k), J(k), G(k)(V), J(k)(V)} 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 + Delta n/n(T)) with (M + Delta n)/n(T). The results for lysozyme fragments can estimate the pI of the whole protein with 1-13% error.

Topological Charge-Transfer Indices: From Small Molecules to Proteins

“…Despite the good results obtained by Pogliani [55][56][57] the isoelectric point pI for 21 amino acids was analyzed by our group [45,47]. The use of (1+ n/n T ) = 1/2 for Arg, 4/3 for Asp and Glu, 2/3 for His and Lys and one for all others improved the fit: The correlation coefficient represents the 96.8% of the one of the correlation of the means (np = 4, r = 0.997).…”

“…The variation of the isoelectric point pI vs. (1+ n/n T ) for the 21 amino acids is shown (Fig. (8), [45,47]). Again, some amino acids result superimposed.…”

“…Last, Torrens and Castellano revised QSPR studies on amino acids and their application to proteins [45]. The VCT indices were applied to the calculation of the pI of 21 amino acids [46] and protein lysozyme [47]; having this last aspects a close relation with coming sections of this manuscript and other manuscripts in this special issue.…”