We are starting off the week taking a look at the science and scientist behind the scenes of the influenza A virus model that won second place in the Society’s 2015 Image contest. The image was created by Heidi Koldsø, a postdoctoral researcher in Mark Sansom’s group in the Department of Biochemistry at Oxford University. Koldsø moved to Oxford from Denmark three years ago on an independent fellowship from the Alfred Benzon foundation. Her research is mainly focused on understanding in details how membrane proteins, which are the largest pharmaceutical target, interact with their surrounding environment. She notes that understanding of not only the membrane proteins but also the lipids surrounding them is of the utmost importance – for example understanding how antimicrobial peptides target bacterial membranes and not human ones. Also, as illustrated in this image, if it is possible to understand how a virus interacts with the cell membrane, scientists can hopefully come up with solutions for better antiviral pharmaceuticals.
The images of the molecular models that captured the attention (and votes) of the 2015 BPS annual meeting attendees were constructed using the molecular visualization program Visual Molecular Dynamics (VMD). Ambient occlusion shading and rendering techniques were applied to the images within VMD. The image depicts an influenza A virus model in close proximity to a coarse grained mammalian plasma membrane model. Due to the large number of particles within these models we used a powerful workstation with lots of memory and a recent graphics card to create the image.
I chose this particular image to submit to the contest because it encapsulates both the achievements we have already made and those that are to come and it was a natural choice as an image that represents the science we study, the hard work we put into it and the potential real world applications it has. Both the project on the outer envelope of the influenza A virus and the large scale cell membranes are very ambitious and time consuming projects and are the result of a lot of hard work from a number of people. This image is the culmination of those two separate endeavours but also the beginning of the next.
When looking at the image, I hope it inspires the viewer to appreciate the current advances in computational modelling and how far we have come in our efforts to probe very real and relevant problems. The image is not only a pretty representation of a simulation as being able to visualize systems at these length scales provide us with unique insight to how these elements might look in vivo. The image does not only give a first glimpse of the molecular details of virus interactions with the membrane but also hopefully provides scientists and the general public with something that they can relate to and will hopefully promote intelligent discussion.
Supporting Scientific Information
The image is a product of the combined efforts of two large ongoing projects in the Sansom research lab at Department of Biochemistry, University of Oxford. The specific research from which the structures are taken involves performing coarse grained molecular dynamics simulations that we run on super-computing resources.
During the last couple of years I have been working on methods to construct complex asymmetric membrane models that allows us to move towards more ‘in vivo’ like systems. Our initial results on studies of complex membranes and the correlation between membrane nano-domains and curvature was published last year (Koldsø et al. PLoS Comput Biol (2014) 10(10): e1003911. doi:10.1371/journal.pcbi.1003911). We have recently started to move toward studying ‘in vivo’ like plasma membrane models at experimental length scales, meaning we are running simulations of systems >100 nm in dimensions and composed or millions of particles.
A complete model of the outer envelope of influenza A virus has recently been revealed, this project was initiated by a previous Postdoc in the Sansom lab,. Daniel Parton (currently working with John Chodera at MSKCC in New York) and has been continued by Tyler Reddy during the last 3 years in Oxford. This Influenza A virion model was recently published in Structure (Reddy et al. (2015) Structure, 23, 584-597).
The image is a result of combining these two projects on the influenza A virus and large scale mammalian cell membranes. We are exploiting the large deformations and curvatures that we observe in the mammalian plasma membrane model to accommodate the virus. This system is extremely complex and large (> 10 M particles) and Tyler and I are currently in the process of equilibrating and optimizing this model. Computational studies of the influenza A virus in close proximity to the cell membrane will potentially provide us with valuable information regarding how viruses enters the human cell during infection.