Conformers Generation¶

#!/usr/bin/env amspython
# coding: utf-8

# ## Initial imports

import os

import matplotlib.pyplot as plt
import numpy as np

from scm.conformers import ConformersJob
from scm.plams import *


# ## Initial structure

molecule = from_smiles("OC(CC1c2ccccc2Sc2ccccc21)CN1CCCC1")
plot_molecule(molecule)


# ## Generate conformers with RDKit and UFF
# The fastest way to generate conformers is to use RDKit with the UFF force field.
#
# Below we specify to generate 16 initial conformers. The final number of conformers may be smaller, as the geometry optimization may cause several structures to enter the same minimum.

# ### Conformer generation settings

s = Settings()
s.input.ams.Task = "Generate"  # default
s.input.ams.Generator.Method = "RDKit"  # default
s.input.ams.Generator.RDKit.InitialNConformers = 16  # optional, non-default
s.input.ForceField.Type = "UFF"  # default


# ### Conformer generation input file

print(ConformersJob(settings=s).get_input())


# ### Run conformer generation

generate_job = ConformersJob(name="generate", molecule=molecule, settings=s)
generate_job.run()


# ## Conformer generation results

# ### Some helper functions


def print_results(job: ConformersJob, temperature=298, unit="kcal/mol"):
    energies = job.results.get_relative_energies(unit)
    populations = job.results.get_boltzmann_distribution(temperature)

    print(f"Total # conformers in set: {len(energies)}")
    dE_header = f"ΔE [{unit}]"
    pop_header = f"Pop. (T = {temperature} K)"
    print(f'{"#":>4s} {dE_header:>14s} {pop_header:>18s}')

    for i, (E, pop) in enumerate(zip(energies, populations)):
        print(f"{i+1:4d} {E:14.2f} {pop:18.3f}")


def plot_conformers(job: ConformersJob, indices=None, temperature=298, unit="kcal/mol", lowest=True):
    molecules = job.results.get_conformers()
    energies = job.results.get_relative_energies(unit)
    populations = job.results.get_boltzmann_distribution(temperature)

    if isinstance(indices, int):
        N_plot = min(indices, len(energies))
        if lowest:
            indices = list(range(N_plot))
        else:
            indices = np.linspace(0, len(energies) - 1, N_plot, dtype=np.int32)
    if indices is None:
        indices = list(range(min(3, len(energies))))

    fig, axes = plt.subplots(1, len(indices), figsize=(12, 3))
    if len(indices) == 1:
        axes = [axes]

    for ax, i in zip(axes, indices):
        mol = molecules[i]
        E = energies[i]
        population = populations[i]

        plot_molecule(mol, ax=ax)
        ax.set_title(f"#{i+1}\nΔE = {E:.2f} kcal/mol\nPop.: {population:.3f} (T = {temperature} K)")


# ### Actual results
#
# Below we see that the **conformer generation gave 14 distinct conformers**, where the highest-energy conformer is 18 kcal/mol higher in energy than the lowest energy conformer.
#
# You can also see the **relative populations** of these conformers at the specified temperature. The populations are calculated from the **Boltzmann distribution** and the relative energies.

unit = "kcal/mol"
temperature = 298


print_results(generate_job, temperature=temperature, unit=unit)
plot_conformers(generate_job, 4, temperature=temperature, unit=unit, lowest=True)  # plot 4 lowest conformers
# plot_conformers(generate_job, 4, temperature=temperature, unit=unit, lowest=False)  # plot 4 conformers from lowest to highest
# plot_conformers(generate_job, [0, 2], temperature=temperature, unit=unit) # plot first and third conformers


# ## Re-optimize conformers with GFNFF
#
# The UFF force field is not very accurate for geometries and energies. From an initial conformer set you can reoptimize it with a better level of theory.
#
# The **Optimize** task performs **GeometryOptimization** jobs on each conformer in a set.
#
# Below, the 10 most stable conformers (within 8 kcal/mol of the most stable conformer) at the UFF level of theory are re-optimized with GFNFF, which gives more accurate geometries.

s = Settings()
s.input.ams.Task = "Optimize"
s.input.ams.InputConformersSet = os.path.abspath(generate_job.results.rkfpath())  # must be absolute path
s.input.ams.InputMaxEnergy = 8.0  # only conformers within 8 kcal/mol at the PREVIOUS level of theory
s.input.GFNFF  # or choose a different engine if you don't have a GFNFF license

reoptimize_job = ConformersJob(settings=s, name="reoptimize")
print(reoptimize_job.get_input())


reoptimize_job.run()


print_results(reoptimize_job, temperature=temperature, unit=unit)
plot_conformers(reoptimize_job, 4, temperature=temperature, unit=unit, lowest=True)


# ## Score conformers with DFTB
#
# If you have many conformers or a very large molecule, it can be computationally expensive to do the conformer generation or reoptimization and a high level of theory.
#
# The **Score** task runs **SinglePoint** jobs on the conformers in a set. This lets you use a more computationally expensive method. Here, we choose DFTB, although normally you may choose some DFT method.

s = Settings()
s.input.ams.Task = "Score"
s.input.ams.InputConformersSet = os.path.abspath(reoptimize_job.results.rkfpath())  # must be absolute path
s.input.ams.InputMaxEnergy = 4.0  # only conformers within 4 kcal/mol at the PREVIOUS level of theory
s.input.DFTB.Model = "GFN1-xTB"  # or choose a different engine if you don't have a DFTB license
# s.input.adf.XC.GGA = 'PBE'                       # to use ADF PBE
# s.input.adf.XC.DISPERSION = 'GRIMME3 BJDAMP'     # to use ADF PBE with Grimme D3(BJ) dispersion

score_job = ConformersJob(settings=s, name="score")
score_job.run()


print_results(score_job, temperature=temperature, unit=unit)
plot_conformers(score_job, 4, temperature=temperature, unit=unit, lowest=True)


# Here, you see that from the conformers in the set, **DFTB predicts a different lowest-energy conformer than GFNFF** (compare to previous figure).

# ## Filter a conformer set
#
# In practice, you may have generated thousands of conformers for a particular structure. Many of those conformers may be so high in energy that their Boltzmann weights are very small.
#
# The **Filter** task only filters the conformers, it does not perform any additional calculations. It can be used to reduce a conformer set so that it is more convenient to work with.
#
# Below, we filter the conformers set to only the conformers within 1 kcal/mol of the minimum.

s = Settings()
s.input.ams.Task = "Filter"
s.input.ams.InputConformersSet = os.path.abspath(score_job.results.rkfpath())
s.input.ams.InputMaxEnergy = 1.0

filter_job = ConformersJob(settings=s, name="filter")
filter_job.run()
print_results(filter_job, temperature=temperature, unit=unit)
plot_conformers(filter_job, 4, temperature=temperature, unit=unit, lowest=True)


# The structures and energies are identical to before. However, the relative populations changed slightly as there are now fewer conformers in the set.

# ## More about conformers
#
# * Try **CREST** instead of RDKit to generate the initial conformer set
#
# * The **Expand** task can be used to expand a set of conformers.