idptools-starling 1.0.0.dev0

Construction of intrinsically disordered proteins ensembles through multiscale generative models

STARLING

Construction of intrinsically disordered protein ensembles through multiscale generative models

Installation

STARLING is currently only available on Github.

We recommend creating a fresh conda environment for STARLING (although in principle there's nothing special about the STARLING environment)

conda create -n starling  python=3.11 -y
conda activate starling

You can then install STARLING from GitHub directly using pip:

pip install git+https://github.com/idptools/starling.git

Or you can clone and install locally as

git clone [e-mail]:idptools/starling.git
cd starling
pip install -e .

NB: Potential Pytorch / CUDA version issues

If you are on an older version of CUDA, a torch version that does not have the correct CUDA version will be installed. This can cause a segfault when running STARLING. To fix this, you need to install torch for your specific CUDA version. For example, to install PyTorch on Linux using pip with a CUDA version of 12.1, you would run:

pip install torch --index-url https://download.pytorch.org/whl/cu121

To figure out which version of CUDA you currently have (assuming you have a CUDA-enabled GPU that is set up correctly), you need to run:

nvidia-smi

Which should return information about your GPU, NVIDIA driver version, and your CUDA version at the top.

Please see the PyTorch install instructions for more info.

Quickstart

The easiest way to use STARLING is the starling command-line tool.

starling <amino acid sequence> -c <number of confomers> --outname my_cool_idr

This will generate an output file call my_cool_idr.starling. To convert this to a PDB trajectory run

starling2pdb my_cool_idr.starling

Or to convert to an xtc/pdb combo run:

starling2xtc my_cool_idr.starling	

starling tool documentation

`usage: starling [-h] [-c CONFORMATIONS] [-d DEVICE] [-s STEPS] [-m METHOD] [-b BATCH_SIZE] [-o OUTPUT_DIRECTORY] [--outname OUTNAME] [-r] [-v] [--num-cpus NUM_CPUS]
                [--num-mds-init NUM_MDS_INIT] [--no-ddim] [--disable_progress_bar] [--info] [--version]
                [user_input]

Generate distance maps using STARLING.

positional arguments:
  user_input            Input sequences in various formats (file, string, list, or dict)

options:
  -h, --help            show this help message and exit
  -c CONFORMATIONS, --conformations CONFORMATIONS
                        Number of conformations to generate (default: 200)
  -d DEVICE, --device DEVICE
                        Device to use for predictions (default: None, auto-detected)
  -s STEPS, --steps STEPS
                        Number of steps to run the DDPM model (default: 25)
  -b BATCH_SIZE, --batch_size BATCH_SIZE
                        Batch size to use for sampling (default: 100)
  -o OUTPUT_DIRECTORY, --output_directory OUTPUT_DIRECTORY
                        Directory to save output (default: '.')
  --outname OUTNAME     If provided and a single sequence is provided, defines the prefix ahead of .pdb/.xtc/.npy extensions (default: None)
  -r, --return_structures
                        Return the 3D structures (default: False)
  -v, --verbose         Enable verbose output (default: False)
  --num-cpus NUM_CPUS   Sets the max number of CPUs to use. Default: 4.
  --num-mds-init NUM_MDS_INIT
                        Sets the number of MDS jobs to be run in parallel. More may give better reconstruction but requires 1:1 with #CPUs to avoid performance penalty. Default: 4.
  --no-ddim             Disable DDIM for sampling.
  --disable_progress_bar
                        Disable progress bar during generation (default: False)
  --info                Print STARLING information only
  --version             Print STARLING version o`nly

Python library

STARLING can generate Ensemble objects which enable deep investigation into ensemble properties using the generate function.

generate function documentation

The generate function is the main entry point for generating distance maps using the STARLING model. This function accepts various input types, generates conformations using DDPM, and optionally returns the 3D structures. You can customize several parameters for batch size, device, number of steps, and more.

To get started, first import the function:

from starling import generate

The generate function is flexible and can take in sequences in multiple formats. Here are a few examples:

# Example 1: Provide a single sequence as a string
sequence = 'MKVIFLAVLGLGIVVTTVLY'

# E is an Ensemble() object
E = generate(sequence, return_single_ensemble=True)


# Example 2: Provide a list of sequences
sequences = ['MKVIFLAVLGLGIVVTTVLY', 'MKVIFLAVLGLGIVVTTVLY']

# returns a dictionary of the Ensemble() objects
E_dict = generate(sequences)

# Example 3: Provide a dictionary of sequences

# returns a dictionary of the Ensemble() objects
sequences = {'seq1': 'MKVIFLAVLGLGIVVTTVLY', 'seq2': 'MKVIFLAVLGLGIVVTTVLY'}

E_dict = generate(sequences)

generate function parameters:

• user_input : str, list, dict
  The input sequences for the model, which can be provided in multiple formats:

  • str: Path to a .fasta file.
  • str: Path to a .tsv or seq.in file (formatted as name\tsequence).
  • str: A single sequence as a string.
  • list: A list of sequences.
  • dict: A dictionary of sequences (name: sequence pairs).

• conformations : int
  The number of conformations to generate. Default is 200. The default is defined in configs.DEFAULT_NUMBER_CONFS.

• device : str
  The device to use for prediction. Default is None, which selects the optimal device:

  • 'gpu' (CUDA or MPS)
  • Falls back to CPU if GPU is unavailable.

• return_single_ensemble : bool
  Flag which, if set to true, means we return a STARLING Ensemble() object instead of a dictionary of ID:Ensemble mapping.

• steps : int
  The number of steps for the DDPM model. Default is 10. The default is defined in configs.DEFAULT_STEPS.

• return_structures : bool
  If True, returns the generated 3D structures. Default is False.

• batch_size : int
  The batch size for sampling. Default is 100 (uses approximately 20 GB memory). The default is defined in configs.DEFAULT_BATCH_SIZE.

• verbose : bool
  If True, prints verbose output during execution. Default is False.

• show_progress_bar : bool
  If True, displays a progress bar during generation. Default is True.

Using an Ensemble class object

Overview

The Ensemble class represents an ensemble of conformations for a protein chain. It is designed to store and manipulate multiple distance maps, and from distance maps, all other structural parameters can be derived

Methods

.rij()

Ensemble.rij(i, j, return_mean=False)

Returns the distance between residues i, and j, either all instantaneous values or the average in return_mean=False is set to True.

.end_to_end_distance()

Ensemble.end_to_end_distance(return_mean=False)

Returns the end-to-end distance, either all instantaneous values or the average in return_mean=False is set to True.

.radius_of_gyration()

Ensemble.radius_of_gyration(return_mean=False)

Returns the radius of gyration, either all instantaneous values or the average in return_mean=False is set to True.

.loacl_radius_of_gyration()

Ensemble.local_radius_of_gyration(start, end, return_mean=False)

Returns the radius of gyration between two specific residues, either all instantaneous values or the average in return_mean=False is set to True.

.distance_maps()

Ensemble.distance_maps(return_mean=False)

Returns the ensemble distance maps, either all instantaneous values (as n x n np.arrays) or the average distance map return_mean=False is set to True.

.contact_map()

Ensemble.contact_map(contact_thresh=11, 
						return_mean=False, 
						return_summed=False):

Using a threshold for contacts defines residues that are in direct contact. If return_mean and return_summed are set to False, the function returns a 3D array of instantaneous contact maps for each conformation. If return_mean is set, the average contract value for each i-j contact is returned (i.e., a value between 0 and 1). If return_summed is set to true, then the summed values are returned instead of the average value.

.build_ensemble_trajectory()

Ensemble.build_ensemble_trajectory(batch_size=100,
        num_cpus_mds=configs.DEFAULT_CPU_COUNT_MDS,
        num_mds_init=configs.DEFAULT_MDS_NUM_INIT,
        device=None,
        force_recompute=False,
        progress_bar=True,

Allows you to build

load_ensemble Function Documentation

STARLING can also easily reload previously generated and saved STARLING ensembles

from starling import load_ensemble
ensemble = load_ensemble('path/to/my_favorite_ensemble.starling')

Copyright

Copyright (c) 2024-2025, Borna Novak, Jeffrey Lotthammer, Alex Holehouse

Acknowledgements

Project based on the Computational Molecular Science Python Cookiecutter version 1.1.