Shake it like a polaroid picture: MD in pyrosetta

> This blog post has been unfinished for two years. So I am posting in the hopes it will spur me to finish it.

The score of a pose reflects how good its interactions are in that static arrangement, a static snapshot. However, given some energy several of these interactions may break and a different conformation is seen. The best way to describe what does 1 kcal/mol mean is that it is the typical strength of a hydrogen bond, but this is rather weak... in fact this is also the average collision energy of water molecules at 37°C, because that is the molar Boltzmann constant times temperature (k_BT/N_A). (At that point in the explanation is it paramount to resist the urge to explain that k_BT coincides with the mean of the Boltzmann distribution describing the energy of collisions as per Maxwell–Boltzmann statistics or else you get that glazed look thermodynamics seems to illicit even in folk that aren't hangover students)

Therefore, hydrogen bonds do come apart and together rather frequently and in some cases these dynamic properties result large scale switching. This cannot really be determined from a static score —even the per residue scores aren't an indication of dynamic properties. So how does one do an MD run in Pyrosetta?

Remote notebooks and Jupyter themes

Jupyter notebooks are great. PyCharm is great for writing a module, but Jupyter notebook let's you test snippets of code really easily. You can add a Julia kernel, run bash and JS snippets and add markdown notes. The even greater thing is that you can run them off remote machines. If you have too many notebooks on different machines it gets confusing, but luckily there is jupyter themes that let's you customise the colours. Here are the different colours.

XML to Pyrosetta: EvolutionaryDynamicsMover as an example

In the previous post I discuss the strategies to use a Pyrosetta class when the documentation lets you down. One topic discussed was the conversion of a Rosetta XML script to Pyrosetta. Here is an example, namely using the EvolutionaryDynamics mover as an example.

Pyrosetta scripting without a manual

I got recently asked how to figure out how to write a Pyrosetta script when there is no example. This is definitely the biggest weakness of Pyrosetta and Rosetta script, but it is not insurmountable. In fact, there is a wealth of information that is hidden that can be mined. Here is how and in the next post, I give an example.

The Freedom unit for molar energy: the foot-pound-force per pound-mole

In computational biochemistry the most commonly used unit is molar energy. The SI unit is kJ/mol (kilojoule per mole), but kcal/mol is also as frequently used —Google enumerates 5.3e6 and 3.8e6 pages for them respectively. Different programs use one or the other, GROMACS uses kJ/mol, while Rosetta uses kcal/mol. They differ by a factor of about 4, the latter has the advantage that 1 kcal/mol is the strength of a hydrogen bond and k_BT/N_A is 0.6 kcal/mol (25°C) or 1. kcal/mol (37°C), while the former being SI sounds more sciency ——and not in the overly obnoxious way as folk who use Kelvin for enzymology.

However, whereas it is not an SI unit, kcal/mol is still very metric and European, after all the unit calorie was introduced by a Frenchman. Therefore, a more American unit is clearly required. Hence the need for the foot–pound-force per pound-mole.

Rosetta/Pyrosetta on a cluster or in the cloud

Due to licensing Rosetta and Pyrosetta cannot be installed via apt-get/pip but has to be downloaded from the Rosetta Commons website. This makes things harder if you are in a colabs notebook, ssh'ed into a machine or running off a remote jupyter notebook. Luckily it actually is straightforward.

5-hydroxytryptophan biosynthesis

 

I was intrigued by a recent article in the journal Chem (link)  entitled "Creation of Bacterial Cells with 5-hydroxytryptophan as a 21st Amino Acid Building Block" by Chen et al. in the group of Han Xiao at Rice University, wherein they make a strain that metabolically produces 5-hydroxytryptophan for genetic code expansion. It is an interesting example of why metabolic engineering is non-trivial and how scientific research does not progress in a logical fashion.