Last month, I posted topics about conformer generation code with rdkit.
RDK_confgen can generate multiple conformers from molfile. This code generates conformers with MMFF94s forcefield. On the other hand recently open force field is very attractive package for these are I think.
Fortunately OpenFF provides example code for conformer energy minimization as CLI tool. So I tested the code.
At first, I made sample molecule for the test.
# from IPython console from rdkit import Chem mol = Chem.MolFromSmiles('C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N') Chem.MolToMolFile(mol, 'januvia.mol')
Then generate conformers with rdk_confgen. After running the code, I could obtain januvia.sdf which has 10 conformers of input molfile.
$ confgen -i januvia.mol -o januvia.sdf --numconf 10
Now ready, run conformer energy minimization code which is provided from openFF github repo. The URL is below.
Down load the example script and type following command. I don’t have OE licence so rdkit is used as backend.
$ python conformer_energies.py -f januvia.sdf Warning: Unable to load toolkit 'OpenEye Toolkit'. The Open Force Field Toolkit does not require the OpenEye Toolkits, and can use RDKit/AmberTools instead. However, if you have a valid license for the OpenEye Toolkits, consider installing them for faster performance and additional file format support: https://docs.eyesopen.com/toolkits/python/quickstart-python/linuxosx.html OpenEye offers free Toolkit licenses for academics: https://www.eyesopen.com/academic-licensing 1 unique molecule(s) loaded, with 10 total conformers C16H15N5O1F6 : 10 conformers Parametrizing C16H15N5O1F6 (may take a moment to calculate charges) Conformer Initial PE Minimized PE RMS between initial and minimized conformer 1 / 10 : 133.220 kcal/mol 123.417 kcal/mol 0.567 Angstroms 2 / 10 : 134.822 kcal/mol 125.368 kcal/mol 0.123 Angstroms 3 / 10 : 136.633 kcal/mol 126.529 kcal/mol 0.343 Angstroms 4 / 10 : 136.635 kcal/mol 126.519 kcal/mol 0.365 Angstroms 5 / 10 : 135.224 kcal/mol 125.566 kcal/mol 0.303 Angstroms 6 / 10 : 135.214 kcal/mol 125.556 kcal/mol 0.307 Angstroms 7 / 10 : 137.509 kcal/mol 127.497 kcal/mol 0.618 Angstroms 8 / 10 : 135.326 kcal/mol 125.955 kcal/mol 0.153 Angstroms 9 / 10 : 137.716 kcal/mol 127.200 kcal/mol 0.621 Angstroms 10 / 10 : 138.217 kcal/mol 128.632 kcal/mol 0.184 Angstroms
After running the code, minimized structures from each conformer was generated as 10 SD files. Running results said that initial structure has higher energy than optimized structure. Here is an example of the result. Purple is an initial structure and green one is optimized.
OpenFF provides some kinds of offxml files https://github.com/openforcefield/openff-forcefields/tree/master/openforcefields/offxml
So I would like to test with different settings and compare results with bio active conformations.
And I would like to know how to run simulate small molecule in solvent with OpenFF. OpenMM can do it but I couldn’t find solution to combine openff forcefiled and openmm forcefiled for solvent such as TIP3P. I’m reading OpenMM document now.
Any comments, advise will be greatly appreciated. ;)