ThomasJewson/Molecular3DLengthDescriptors

A 3D conformational based molecular descriptor set for use in QSPR and Machine Learning.

Molecular3DLengthDescriptors

Introduction

The Molecular3DLengthDescriptors package can do the following:

1. Calculates the lowest energy 3D conformer of a molecule using RDKit's UFF and MFF94 force fields.
2. Converts an array of coordinates into a set of lengths: longest, medium and shortest.
3. Descriptors can be calculated from these lengths.

Applications

You can use this tool to do the following:

• Calculate these descriptors for a machine learning project from 2D SMILES input.
• Calculate these descriptors using crystallogaphic molecular coordinates exported from a database such as the CSD.
• Calculate these descriptors using coordinates calculated via another method (eg: GROMACS, BALLOON, CONFAB... etc)

Installation

Installation of this package requires Python 3+.

You can install this package two ways...

via pip:

pip install Molecular3DLengthDescriptors

(https://pypi.org/project/Molecular3DLengthDescriptors/)

Or manually, by placing the Molecular3DLengthDescriptors folder within

~/.local/lib/pythonX.X/site-packages

The rdkit and numpy libraries are dependencies for this package. Install them with the following:

conda install numpy

https://www.rdkit.org/docs/Install.html

How Molecular3DLengthDescriptors module works

1. Import package

import Molecular3DLengthDescriptors as md

2. Calculate 3D coordinates of 2D molecule

This code is based off Wicker et al's nConf20 descriptor (10.1021/acs.jcim.6b00565).

from rdkit.Chem import MolFromSmiles

smiles = "O=c1cccc(/C=C/c2ccccc2)o1"
mol_2D = MolFromSmiles(smiles)
mol_2D

cc = md.Lengths.ComputeCoordsFrom2D()
coordinates = cc.GetCoords(mol_2D)
coordinates

array([[ 4.19392625, -2.10217421,  1.20758067],
       [ 3.77614639, -1.12343758,  0.59832016],
       [ 4.72136167, -0.18159364, -0.02926615],
       [ 4.27935864,  0.88880918, -0.69605956],
       [ 2.87057618,  1.13819338, -0.81141094],
       [ 2.00047091,  0.2903415 , -0.24586024],
       [ 0.56197146,  0.46799511, -0.31472371],
       [-0.34101042, -0.35981258,  0.23919665],
       [-1.81020273, -0.21901879,  0.19470342],
       [-2.47547343,  0.83154283, -0.45235907],
       [-3.87295236,  0.9032948 , -0.45516855],
       [-4.62630912, -0.07414675,  0.18888447],
       [-3.98359642, -1.12449045,  0.8365183 ],
       [-2.58741845, -1.19525503,  0.83872962],
       [ 2.44345336, -0.85157198,  0.4663684 ]])

3. Calculate the lengths of the 3D molecule

The covariance of the molecular coordinates is calculated. Then eigenvectors and eigenvalues from the covariance matrix is calculated. The eigenvectors will be aligned in directions of most variance, least variance and right angles to both of those. Therefore, if the square root of the eigenvalues is taken these values will now be back on the same unit scale as the coordinates and hence can be interpreted as the lengths of the molecule.

lengths = md.Lengths.GetLengthsFromCoords(coordinates)
lengths

[0.0001053619852081641, 1.124146300889793, 3.3578154223541476]

4. Calculate descriptors

You can calculate individual descriptors:

print(md.Descriptors.Flatness(lengths))
print(md.Descriptors.Cubeularity(lengths))
print(md.Descriptors.Plateularity(lengths))
print(md.Descriptors.ShortOverLong(lengths))
print(md.Descriptors.MediumOverLong(lengths))

0.0001053619852081641
1.0504929488912333e-05
35825.784590642164
3.1378134875053776e-05
0.334785019273531

Or all at once:

md.Descriptors.CalcAllDesc(lengths)

{'Flattness': 0.0001053619852081641,
 'Cubeularity': 1.0504929488912333e-05,
 'Plateularity': 35825.784590642164,
 'ShortOverLong': 3.1378134875053776e-05,
 'MediumOverLong': 0.334785019273531}

Explainations of descriptors

To explain what the descriptors mean, place help(...) around the function to output the docstring.

help(md.Descriptors.ShortOverLong)

Help on function ShortOverLong in module Molecular3DLengthDescriptors.Descriptors:

ShortOverLong(lengths)
    A measure of how cubic a molecules is.
    
    0 means either a needle or plate shape.
    1 means perfect cube
    
    ShortOverLong = Shortest / Longest

help(md.Descriptors.CalcAllDesc)

Help on function CalcAllDesc in module Molecular3DLengthDescriptors.Descriptors:

CalcAllDesc(lengths)
    Flattness => Shortest length
        Measure of how flat a molecules is.
    
    Cubularity => (Shortest*Medium*Longest)/(Longest)**3
        1 is a perfect cube. 
    
    Plateularity => (Medium*Longest)/ Shortest
        Larger value, more 2D plate-like.
        
    ShortOverLong => Shortest / Longest
        1 is perfect cube, 0 is needle or plate-like
        
    MediumOverLong => Medium / Longest
        1 is perfect plate-like shape, 0 is perfect needle shape

Reference

If you use this package please feel free to reference us with:

Jewson, T., & Cooper, R. I. (2021). Molecular3DLengthDescriptors (1.0.0). https://github.com/ThomasJewson/Molecular3DLengthDescriptors

Or add this BibTeX entry to your .bib library:

@misc{Jewson2021,
author = {Jewson, Thomas and Cooper, Richard I.},
title = {{Molecular3DLengthDescriptors}},
url = {https://github.com/ThomasJewson/Molecular3DLengthDescriptors},
year = {2021}
}