Principal Component Analysis of a Conotoxin Delineates the Link among Peptide Sequence, Dynamics, and Disulfide Bond Isoforms.

Replica exchange molecular dynamics (REMD) and subsequent principal component analysis (PCA) of the dynamical modes of α-conotoxins, GI and its two mutants, in water and an aqueous biocompatible ionic liquid, 1-ethyl-3-methyl-imidazolium acetate (50%, v/v), provide perceptions into how the mutations affect the global correlated motions in the peptide backbone, eventually ending up influencing the combination of disulfide links in such multiple cysteine-containing venom toxins. Region-wise breakup of the contribution of the three peptides to the first two principal components (PCs) reveals disparate dynamical patterns in water and a water-ionic liquid mixture. Additionally, K-means clustering within the conformation space spanned by PC1 and PC2 compares and contrasts the different peptide-solvent systems, sorting further the disulfide bond isoforms into specific clusters. In each cluster, and also in a particular disulfide bond isoform, an estimation of the amino acid block loadings toward PC1 and PC2 helps relate the mutations in the GI sequence to targeted synthesis of a given isoform in a given solvent system.