## Background

One of the methods of epigenetics is DNA-methylation. While not technically a "post-translational modification", it is conceptually similar and so uses Rosetta's EnzymaticMovers framework.

The DNA_methylation application allows a user to simulate the action of a virtual DNA methyltransferase (Mtase) enzyme on a "substrate" — the loaded .pdb structure, which contains DNA residues. The virtual transferase may be a biologically real transferase or entirely hypothetical or constructed.

## Description

This application is currently a simple command-line wrapper for the DNAMethyltransferaseMover. It simulates the activity of a virtual Mtase on a Pose by modifying (a) DNA residue(s) at biologically relevant sequon positions into a METHYLATED_NA VariantType. It performs no further refinement or algorithmic steps.

One can use the DNA_methylation application to quickly methylate DNA at biologically relevant nucleobase positions, depending on the virtual enzyme selected for the application. Further applications can be used to refine the output structure(s) in preparation for other protocols.

## Options

General Options

Froup Flag Description Type
in:path s Name of the .pdb file to process. String
enzymes species Set the species name of this simulated enzyme. The default value is h_sapiens. String
enzymes enzyme Set the specific enzyme name of this simulated enzyme. The default value is generic. String
enzymes efficiency Set the efficiency of the this simulated enzyme, where 1.0 is 100%. The default value is read from the database. Real
out nstruct Number of times to process each input .pdb file. Integer

Details Setting the species name limits the behavior of the simulated methyltransferase used in this application to consensus sequences used by the homolog found in the given species. A species name must be in the format e_coli or h_sapiens, (note the underscores,) which must also correspond to a directory in the Rosetta database, e.g., database/virtual_enzymes/DNA_methyltransferases/h_sapiens/. If not set, h_sapiens is assumed.

If set, the simulated enzyme used in this application will use specific enzymatic details for this reaction from the database. If the species name has not been set, a "generic" enzyme from the DNA methyltransferase family is assumed. An enzyme name must be as listed in an appropriate enzyme file in database/virtual_enzymes/DNA_methyltransferases/<species_name_>.

The generic H. sapiens DNA methyltransferase is a C5 Mtase that methylates the deoxycytidine residue of any CpG sequons on a struture with 100% efficiency.

See EnzymaticMovers#Enzyme Data Files for information on how to format your own enzymatic data for other DNA methyltransferases.

## Sample Command Line

DNA_methylation -s input/1ABC.pdb -enzymes:species h_sapiens -enzymes:efficiency 0.33 -nstruct 5

## Code & Demo

The DNA_methylation application can be found in /Rosetta/main/source/src/apps/public/post-translational_modification/DNA_methylation.cc.

A demo for the DNA_methylation application can be found in /Rosetta/main/tests/integration/tests/DNA_methylation/.

## Contact

Labonte JWLabonte@jhu.edu