Role of the Cation-π Interaction in Therapeutic Proteins: A Comparative Study with Conventional Stabilizing Forces

Abstract

The cation-π interaction is an important, general force for molecular recognition in biological receptors. In this study, we have analyzed the energy contribution resulting from cation-π interactions in the set of therapeutic proteins. The contribution of cation-π interacting residues in secondary structure involvement, solvent accessibility, stabilization centers, stabilizing residues and conservation score has been evaluated. Secondary structure of the cation-π involving residues shows that, Arg and Lys prefers to be in strand. Among the π residues, Phe prefer to be in coil, Tyr prefers to be in strand and Trp prefer to be in helix. Among the cation-π interacting residues Arg and Lys were in the exposed regions. Phe and Tyr were in the partially buried region and Trp in the fully buried region. Stabilization centers for these proteins showed that all the five residues found in cation-π interactions are important in locating one or more of such centers. The contribution of stabilizing residues in the cation-π interactions was analyzed. Further, the study shows that, 43 percent of the amino acid residues that are involved in cation-π interactions might be conserved in therapeutic proteins. The comparison between the conventional and nonconventional interactions in the data set, clearly depict the significance of cation-π interaction in the stability of therapeutic proteins. On the whole, the results presented in this work will be very useful for understanding the contribution of cation-π interaction to the stability of therapeutic proteins.