Genome reduction is a common phenomenon in intracellular endosymbionts, parasites and pathogens. Because of substantial gene and functional loss, genome reduction precipitates reliance on the host for nutrition and energy supplies

Technologies that measure characteristics of large families of cellular molecules (e.g., genes, proteins, metabolites), have been collectively described by using the suffix ‘-omics’at the end of the name of the characteristic measured. Etymology of the suffix comes from the Latin suffix ‘-ome’, derived from mass or many.

Botulinum Neurotoxins (BoNTs) bind the neuronal membrane of the host cell via dual interactions with both protein receptors and gangliosides. In order to decipher the molecular determinants for recognition of cell surface protein receptor synaptotagmins II (Syt-II) by the BoNT serotype B (BoNT/B), a high-level quantum chemical analysis was performed, on the basis of the 2.15 Å resolution x-ray crystal structure of the BoNT/B – Syt-II complex. The work resulted in the discovery of two interfaces of molecular recognition; the amphipathic α-helix of the protein receptor Syt-II interacts with BoNT/B by forming a hydrophobic interface on one side of the helix and a hydrophilic interface on the other side. The hydrophobic interface consists of residues Phe47, Leu50, Phe54, Phe55 and Ile58 of Syt-II interacting with residues Trp1178, Tyr1181, Tyr1183, Phe1194 and Phe1204 of BoNT/B. The hydrophilic interface is composed of residues Lys53 and Glu57 of Syt-II interacting with residues Lys1113, Asp1115, Ser1116 and Lys1192 of BoNT/B. Intermolecular interaction energies between BoNT/B and Syt-II were calculated by means of the supermolecular approach at the MP2 level with subsequent solvation energy correction. It was found that the energetic contribution of the hydrophobic interface toward binding of BoNT/B with Syt-II (-9.49 kcal/mol) is much stronger than that of the hydrophilic interface (-2.58 kcal/ mol). Furthermore, pair-wise intermolecular interaction analysis led to the findings that π-π stacking interactions among aromatic residues are the major molecular determinants for recognition of cell surface protein receptor Syt-II by the botulinum neurotoxin BoNT/B. These findings are significant since it was widely believed that the extreme toxicities of BoNTs have a lot to do with the high affinity and specificity of their binding to the neuronal membrane. It is expected that a detailed understanding of the intermolecular interactions responsible for the extreme specificity of molecular recognition between BoNT and its protein receptor as reported here will have far reaching implication for not only the rational design of potent protein toxin inhibitors targeting toxin-protein receptor binding interface but also the development of more suitable therapeutic neurotoxins.