Forced unbinding of oseltamivir from H5N1 neuraminidase.
2010-09-23T02:22:13Z (GMT) by
<p>Shown are timelapsed snapshots of oseltamivir along its exit pathway on the electrostatic surface of avian H5N1 neuraminidase during simulation <i>simSMD1</i>. At 0 ns (A), oseltamivir is stably bound within the SA binding pocket, as also seen in <i>simEQ1</i>. Application of force ruptures the stabilizing hydrogen bonds between H5N1 and oseltamivir (see also <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000939#pcbi-1000939-g002" target="_blank">Figure 2</a>), drawing the drug away from the SA binding site within 10 ns, as shown in B. Over the next 2.5 ns of pulling, oseltamivir follows the charged binding funnel (shown in C) until it is completely free of the protein binding pocket after 15 ns, as shown in D. Despite application of force directed straight out of the SA binding site, the drug follows a lateral unbinding path through the negatively charged funnel shown in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000939#pcbi-1000939-g001" target="_blank">Figure 1</a>.</p>