Molecular Dynamics Analysis of Antibody Recognition and Escape by Human H1N1 Influenza Hemagglutinin


How did you compose this image?

The cover art–composed of the 1918 antibody (Ig-2D1) binding to the 2009 hemagglutinin (09HA)–is generated from visual molecular dynamics and enhanced in GIMP (GNU image manipulation program). The protein at the bottom is the 09HA, colored by residue name, and the protein on top is the antibody, colored in grey. The protein system was solvated in a water box and simulated in NAMD. We aimed to study the interactions between the antibody and antigen under simulated physiological conditions. We were inspired by the idea that inside the body, everything is dark, but the antibody and antigen complex is our “super star” and our study of interest; we let it “glow” in the dark as a symbol of human understanding of the mechanism of the interactions. The protein complexes are typically surrounded by water molecules, signified by the bubbles or water droplets. The bubbles reflect the complex and echoes the advances in knowledge and celebration of science.

How does this image reflect your scientific research?

The human immune response to the influenza virus is a fascinating area of research, and the thrust of our research aims to provide detailed molecular-level understanding of the mechanism of interactions between antibodies and antigens through computational simulation. In this particular study, we have, to our knowledge, uncovered novel understandings of how mutations in the influenza HA protein, in particular, the 2009 pandemic H1N1 HA, may confer immune escape from human defense. In particular, water molecules may contribute to weakening the interactions between antibodies and antigens in conjunction with the mutations.

Can you please provide a few real-world examples of your research?

Computational simulation plays a key role in advancing our understanding of human-pathogen interaction, and molecular dynamics simulations have been our main tool of investigation into various aspects of the influenza virus. For example, these techniques have been applied in the design of new inhibitors against influenza neuraminidase, and the current study explores the use of molecular dynamic simulation to compare antibody binding affinities, and could have immediate impact on antibody design and engineering.

How does your research apply to those who are not working in your specific field?

Atomic-level physics-based simulations are accurate enough to provide predictive hypotheses for experimental validation. The techniques are now applicable to researchers studying protein-protein and protein-small molecule interactions in other fields. Continued advances in computing technology will continue to enhance the realism of the modeled experimental systems, driving our “computational microscope” toward better understanding of natural phenomena and ultimately leading to better and safer therapeutics for humans.

Do you have a website where our readers can view your recent research?

– Pek Ieong, Rommie E. Amaro, Wilfred W. Li


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