A Molecular View of HIV Therapy [video]

Pretty cool visualization.<p>HIV integrase is used a lot in many gene therapies. It is very good at &#x27;inserting a genetic payload&#x27; into a human&#x27;s genome. So we often co-opt it to insert desirable sequences (see sickle-cell disease discussion [1]). Everyone&#x27;s favorite Cas9 is able to cut DNA at particular sequences, but is not of much help actually getting a payload to load inline at the location that it homes in on. The HIV integrase is about the opposite, it&#x27;s great at getting a payload to load inline, but it inserts relatively randomly (which is dangerous - an insertion at random spots could put code in the middle of an important oncogene). Ideally we&#x27;d have a kind of hybrid integrase&#x2F;Cas9 that is able to <i>both</i> target, and insert a payload dna inline into the genome - at a specific site only.<p>The therapies described in the video are all small molecules. Some of the more interesting, newer therapies however are instead protein mimics that actually play a higher-level role in &#x27;deceiving&#x27; rather that just trying to &#x27;jam&#x27; the virus (see the eCD4-IG synthetic protein [2]).<p>[1] <a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=13781549" rel="nofollow">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=13781549</a><p>[2] <a href="https:&#x2F;&#x2F;serotiny.bio&#x2F;notes&#x2F;proteins&#x2F;ecd4ig&#x2F;" rel="nofollow">https:&#x2F;&#x2F;serotiny.bio&#x2F;notes&#x2F;proteins&#x2F;ecd4ig&#x2F;</a>

This is a really amazing visualization. One of the things that I like about it is that the visualization shows representative random, nonproductive interactions (the other molecules that bounce off of the enzymes, for example) and the enzymes don&#x27;t typically &quot;magically go straight to&quot; where they&#x27;re supposed to do, they&#x27;re often doing a little bit of fumbling around first.<p>This is in contrast to a videos like this one, where the molecules move with a purpose: <a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=bbbbbcAeCa4" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=bbbbbcAeCa4</a><p>or this one, where you watch protein helixes magically self-assemble by zooming into exactly where they needed to be - a process so statistically unlikely it boggles the mind,<p><a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=B_zD3NxSsD8&amp;list=PLj1EIndZcOLKapv29qpv5J-WMYkPDEb1Y&amp;t=2m42s" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=B_zD3NxSsD8&amp;list=PLj1EIndZcO...</a>

Lovely. A similar style of animation to that of Drew Berry (also the sound-design is similar). I wonder if the rotations of the atomic chains are accurate: Drew Berry&#x27;s visualizations show some of the translational thermal noise, but little rotational noise.<p>What&#x27;s hard in these animations is to depict the mechanisms without using the motion-graphics equivalent of intentional stance (&quot;x evolved <i>for</i> y&quot;). Molecules don&#x27;t have intentions, only electric fields (which are never shown) by which they move. That&#x27;s not including quantum effects...anyway many molecular animations give the false impression that the molecules have agency.

Last week there was a study on ice baths. You can&#x27;t really find clear signal for more than 24 hours. Info is moving to fast.