DiscTransformation: A software to sample and build models for Quasi-2D systems

Disctransformation Background

Disctransformation is a software package which packs the 2D objects in a given geometry. The 2D objects can be approximations of molecular objects (entire molecules, domains of molecules, etc.) whose size can be altered by the user. The objects are packed in accordance with a user-specified arrangement that follows a particular interaction topology.

Sampling algorithms such as Monte Carlo, Divide and conquer can be used in conjunction with Disctransformation to get the optimal packing of the objects. Current version supports the brute-force sampling and includes a wrapper for sampling.

Disctransformation can be used for the development of new model representations and combining various scoring schemes to solve the packing optimization problems. The result can be visually inspected and evaluated using the output written by the code.

Relevance to the molecular architectures

Disctransformation is useful in instances where molecular interactions can be envisaged as quasi-2D problems, or when the focus of the problem is on a cross-section of the structure. For instance, the packing of helices in a bundle. The modes of interactions between helices, each of which could be approximated by a disc, are obtained from experimental sources (e.g., FRET or chemical cross-linking). DiscTransformation has the capacity to distinguish between different vertical orientations of the helices (N above and C below or vice versa could be denoted as parallel and anti-parallel orientations respectively in the input file). The program is hence a quick visual and sampling guide to the possible solutions to the molecular arrangement problem. For further analysis, other (external) scoring schemes could be used to distinguish between the different solutions.

Installation

There is no need to Install the Disctransformation. You can directly use it either from the command line or directly by accessing api.

Open index.html for Documentation and API

https://neeleshsoni21.github.io/disctransformation/doc/build/html/index.html

Running Disctransformation

See API in index.html.

An example of the code that execute DiscTransformation on the built-in example pdb

import Disctransformation as DT
DT.example_single_run()

Above code will take default input and generate output in the output directory listed in the input file. Default input directory is Disctransformation/example/input/.

Following are the default input and output files:

1. gpcr_dimer.txt : Disctransformation default input file to illustrate single run. See Input file format for more details.

2. DT_GPCR_Dimer.ps : Default output file corresponds to the above input file. This post-script file displays the orientation of the Quasi-2D model.

Above command is equivalent to the following command:

DT.example_single_run(
    input_dtfile = './Disctransformation/example/input/gpcr_dimer.txt')

Above Disctransformation run, uses the gpcr_dimer.txt as input to construct the gpcr dimer model with the given parameters. The model assumes whiole gpcr as a 2D disc aligned on the z-axis. Parameters for how to assemble the dimer can be provided in the input file. See Input-file format for more details.

To run the Disctransformation with the pdb coordinates, provide the pdb file as an input file as follows:

DT.example_single_run_withpdb(
    input_dtfile = './Disctransformation/example/input/gpcr_dimer.txt',
    input_pdb = './Disctransformation/example/input/GPCR_Helices.pdb',
    output_dir = './Disctransformation/example/output_gpcr/')

Above command generates a Quasi-2D model in both ps and pdb format. The models will be generated in the output_gpcr. Generating PDB models are generally very slow. If you do a large smapling (see below), then avoid generating pdb models duriong the sampling. Instead save the Disctransformation input file (see Input-file format description) for all samples, then choose your model (either by visualizing PS formatted file or using scoring functions!) and then rerun the Disctransformation with the choosen input file.

To construct the gpcr trimer, use the gpcr_trimer input file. The illustrates how to make a trimer or n-mer model:

DT.example_single_run(
    input_dtfile = './Disctransformation/example/input/gpcr_trimer.txt')

To construct the gpcr trimer with pdb coordinates use the following:

DT.example_single_run_withpdb(
    input_dtfile = './Disctransformation/example/input/gpcr_trimer.txt',
    input_pdb = './Disctransformation/example/input/GPCR_Helices.pdb',
    output_dir = './Disctransformation/example/output_gpcr/')

All above Disctransformation runs are single runs with a given input file. This means you need to provide the configuration of the model and Disctransformation just builds it. However, in most cases, you wouldn’t know the model configuration (else why would you need a Disctransformation!!). Disctransformation can sample a large number of models very efficiently (given you dont generate PDB models during sampling!).

Use the following wrapper over Disctransformation to do the sampling and scoring for a trimer with single interacting mode ‘A’ between the discs. See Input-file format for details of how to coarse/fine grain sampling.

DT.example_sampling_run(
    input_dtfile = './Disctransformation/example/input/gpcr_trimer_sample_1mode.txt',
    input_pdb = './Disctransformation/example/input/GPCR_Helices.pdb',
    output_dir = './Disctransformation/example/output_gpcr_ensemble_1mode/')

Above example samples all possible models with the resolution specified in the input file. All models will be generated and stored in the output directory. A sampling list is also generated in the output directory for users for debug purpose. This file can be used to coarse/fine grain sampling.

Use the following to sample and score a trimer with two interacting modes ‘A’ and ‘B’ between discs.

DT.example_sampling_run(
    input_dtfile = './Disctransformation/example/input/gpcr_trimer_sample_2mode.txt',
    input_pdb = './Disctransformation/example/input/GPCR_Helices.pdb',
    output_dir = './Disctransformation/example/output_gpcr_ensemble_2mode/')