WEBVTT

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Hi, I'm Blaine Mooers.

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I'm going to be talking about

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the use of molecular graphics in Org

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for the purpose of doing 

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reproducible research in structural biology.

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I'm an associate professor of biochemistry

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and microbiology at the University of Oklahoma 

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Health Sciences Center in Oklahoma City.

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My laboratory uses X-ray crystallography

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to determine the atomic structures

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of proteins like this one

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in the lower left, and of nucleic acids

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important in human health.

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This is a crystal of an RNA,

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which we have placed in this

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X-ray diffraction instrument.

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And after rotating the crystal

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in the X-ray beam for two degrees,

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we obtain this following diffraction pattern,

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which has thousands of spots on it.

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We rotate the crystal for over 180 degrees,

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collecting 90 images to obtain all the data.

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We then process those images

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and do an inverse Fourier transform

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to obtain the electron density.

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This electron density map has been

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contoured at the one-sigma level.

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That level's being shown by

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this blue chicken wire mesh.

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Atomic models have been fitted

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to this chicken wire.

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These lines represent bonds between atoms,

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atoms are being represented by points.

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And atoms are colored by atom type,

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red for oxygen, blue for nitrogen,

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and then in this case,

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carbon is colored cyan.

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We have fitted a drug molecule

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to the central blob of electron density

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which corresponds to that active site

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of this protein, which is RET Kinase.

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It's important in lung cancer.

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When we're finished with model building,

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we will then examine 

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the result of the final structure

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to prepare images for publication

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using molecular graphics program.

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In this case,

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we've overlaid a number of structures,

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and we're examining the distance between

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the side chain of an alanine

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and one or two drug molecules.

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This alanine sidechain actually blocks

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the binding of one of these drugs.

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The most popular program

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for doing this kind of analysis

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and for preparing images

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for publication is PyMOL.

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PyMOL was used to prepare these images

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on the covers of these featured journals.

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PyMOL is favored because

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it has 500 commands

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and 600 parameter settings

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that provide exquisite control

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over the appearance of the output.

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PyMOL has over 100,000 users,

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reflecting its popularity.

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This is the GUI for PyMOL.

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It shows in white the viewport area

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where one interacts 

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with the loaded molecular object.

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We have rendered the same RET kinase

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with a set of preset parameters

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that have been named "publication".

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The other way of applying

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parameter settings and commands

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is to enter them at the PyMOL prompt.

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Then the third way is to load and run scripts.

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PyMOL is actually written in C for speed,

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but it is wrapped in Python for extensibility.

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In fact, there are over 100 articles

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about various plugins and scripts 

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that people have developed

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to extend PyMOL for years.

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Here's some examples 

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from the snippet library that I developed.

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On the left is a default

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cartoon representation of a RNA hairpin.

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I find this reduced representation

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of the RNA hairpin to be too stark.

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I prefer these alternate ones

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that I developed.

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So, these three to the right of this one

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are not available through

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pull downs in PyMOL.

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So why developed a PyMOL

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snippet library for Org?

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Well, Org provides great support 

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for literate programming,

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where you have code blocks

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that contain code that's executable,

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and the output is shown

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below that code block.

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And then you can fill 

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the surrounding area in the document

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with the explanatory prose.

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Org has great support 

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for editing that explanatory prose.

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Org can run PyMOL through PyMOL's Python API.

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One of the uses of such an Org document

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is to assemble a gallery of draft images.

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We often have to look at

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dozens of candidate images 

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with the molecule in different orientations,

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different zoom settings,

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different representations,

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different colors, and so on.

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And to have those images along with…,

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adjacent to the code

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that was used to generate them,

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can be very effective for

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further editing the code

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and improving the images.

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Once the final images have been selected,

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one can submit the code

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as part of the supplemental material.

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Finally, one can use the journal package

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to use the Org files as

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an electronic laboratory notebook,

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which is illustrated with molecular images.

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This can be very useful

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when assembling manuscripts

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months or years later.

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This shows the YASnippet pull down

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after my library has been installed.

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I have an Org file open,

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so I'm in Org mode.

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We have the Org mode submenu,

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and under it, all my snippets

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are located in these sub-sub-menus

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that are prepended with pymolpy.

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Under the molecular representations menu,

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there is a listing of snippets.

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The top one is for the ambient occlusion effect,

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which we're going to apply

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in this Org file.

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So these lines of code were inserted after,

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as well as these flanking lines

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that define the source block,

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were inserted by clicking on that line.

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Then I've added some additional code.

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So, the first line defines

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the language that we're using.

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We're going to use

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the jupyter-python language.

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Then you can define the session,

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and the name of this is arbitrary.

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Then the kernel is our means

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by which we gain access

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to the Python API of PyMOL.

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The remaining settings apply to the output.

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To execute this code 

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and to get the resulting image,

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you put the cursor inside this code block,

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or on the top line,

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and enter Control c Control c (C-c C-c).

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This shows the resulting image

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has been loaded up.

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It takes about 10 seconds for this to appear.

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So the downside of this is

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if you have a large number of these,

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the Org file can lag quite a bit

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when you try to scroll through it,

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so you need to close up these result drawers,

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and only open up the ones 

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that you're currently examining.

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These are features I think

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are important in practical work.

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So, the plus is, a feature that's present,

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minus is absent.

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I think tab stops and tab triggers

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are really important.

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Triggers are important for

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the fast assertion code,

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tab stops are important for

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complete, accurate editing of code.

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I already addressed the rendering speed

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and scrolling issue.

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I think the way around this

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is just to export the Org document to a PDF file

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and do your evaluation of different images 

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by examining them in the PDF 

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rather than the Org file.

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The path to PDF is lightning fast in Emacs

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compared to Jupyter,

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where it's cumbersome in comparison.

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This is a snapshot of my initialization file.

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These parts are relevant to doing this work.

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A full description of them

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can be found in the README file

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of this repository on GitHub.

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I'd like to thank the

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Nathan Shock Data Science Workshop

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for feedback during presentations

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I've made about this work.

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And I would also like to thank

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the following funding sources for support.

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I will now take questions. Thank you.

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[captions by Blaine Mooers and Bhavin Gandhi]