A stepwise docking molecular dynamics approach for simulating antibody recognition with substantial conformational changes.

Conformational changes or rearrangements are common events during inter-biomolecular recognition. Tracking these changes are essential for exploring the allosteric mechanism and it is usually achieved by molecular dynamics simulation . We previously identified a broad-neutralizing antibody against H5 influenza virus, 13D4, and solved the crystal structures of the free 13D4 Fab and its complex with hemagglutinin (HA).

Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody.

Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses.

Identification of Strategic Residues at the Interface of Antigen-Antibody Interactions by In Silico Mutagenesis.

Structural information pertaining to antigen-antibody interactions is fundamental in immunology, and benefits structure-based vaccine design. Modeling of antigen-antibody immune complexes from co-crystal structures or molecular docking simulations provides an extensive profile of the epitope at the interface; however, the key amino acids involved in the interaction must be further clarified, often through the use of experimental mutagenesis and subsequent binding assays. Here, we describe an in silico mutagenesis method to identify key sites at antigen-antibody interfaces, using significant increase in pH-dependency energy among saturated point mutations.

A shared N-terminal hydrophobic tail for the formation of nanoparticulates.

Aim: Nanoparticulate design is important for the production of nanotechnological materials and passive immunogens. Using lessons from our hepatitis E vaccine, we herein design protein-based nanoparticles through incorporation of an N-terminal hydrophobic tail (NHT, located on HEV ORF2 aa368-460).

Materials & Methods: Flu HA1, HIV gp41/gp120/p24, HBsAg and HPV16 L2 were fused with NHT, expressed in Escherichia coli and subjected to self-assembly in vitro.