Similarity search combined with DFT screening co-assembles binary molecular combinations
Step 1. Shape similarity screening (Small molecule similarity screening can be performed using Discovery Studio)
1.1 Target molecule
Upload the 3D structure of aristolochic acid and berberine respectively.
1.2 Similarity screening
Use Select Subset Libraries module to Find Similar function for Similarity screening based on small molecule fingerprints and properties. The minimum similarity score is set to 0.5, and Similarity Coefficient is set to Tanimoto method. FCFC_6 is used in Use Properties.
1.3 Visual screening
Further calculate molecular properties such as AlogP, hydrogen bond donor, hydrogen bond acceptor, and rotatable bond, and view 3D structures in the Discovery Studio graphical interface to visually screen groups with hydrogen bond, electrostatic, and π-π interactions. The data is then exported to excel and molecules with similarities greater than 0.7 are deleted.
1.4 Heat mapping
The top 20 molecules (AA_DATA.xlsx or BB_DATA.xlsx) of aristolochic acid/berberine were selected and heat_mapping.ipynb was used to draw the similarity heat mapping.
Step 2. DFT calculation
2.1 Generates a binary conformation
You can find the data.xlsx file under the DFT/data path, which contains the molecule name and smiles.
Next, you can run the binary_conformation.ipynb script step-by-step to generate the binary conformation. Note that this script is executed by calling an external tool to genmer. If you have deployed the software correctly, you can change the path to it in this line of code to “subprocess.run(”/home/cptd/Documents/Molclus/fangbo/genmer” , shell=True)”. genmer.ini is the configuration file for the genmer tool, and you usually don't need to modify it if you want to generate 100 conformations. More information and instructions on the use of the genmer tool can be found on this website (http://www.keinsci.com/research/molclus.html), and when you use the tool, be sure to cite Tian Lu, Molclus program, Version x.x, http:/ /www.keinsci.com/research/molclus.html (accessed month day, year). The script produces a file atom_num_name.xlsx and folders AAAA, BBBB, and genmer_mole. atom_num_name.xlsx contains the atomic number of each molecule, the folders AAAA and BBBB hold the 3D structure of the molecule, and the genmer_mole folder holds each pair of binary conformations.
2.2 Conformational search calculations
Next, you can use the batch_molclus_orca.ipynb script to calculate, and the components that are computed incorrectly will be saved as a none.csv file. After that, you can correct the error according to the error message, and then call the error_batch_molclus_orca.ipynb script to calculate.
After the DFT task is calculated, you can specify the IGMH component you want to calculate based on the binding energy results. The IGMH calculation is included in batch_molclus_orca.ipynb. When you have calculated the IGMH, you will generate the *.cub file, which needs to be visualized using vmd, which can be found at http://sobereva.com/621.
2.3 Bind Heat mapping
This section of the drawing can be found on heat_mapping.ipynb.
Declaration: If you use this script, be sure to cite the following literature. The script only provides an interface, and there is no secondary development of the program. If there is any problem with the script, please contact me in time (yunitcon@yeah.net).
Reference: [1] Tian Lu, Molclus program, Version x.x, http://www.keinsci.com/research/molclus.html (accessed March 10, 2024)
[2] Y. Ma, Q. B. Mou, D. Y. Yan, X. Y. Zhu, View 2020, 1, 20200062.
[3] A. P. Bento, A. Hersey, E. Félix, G. Landrum, A. Gaulton, F. Atkinson, L. J. Bellis, M. De Veij, A. R. Leach, J. Cheminformatics 2020, 12, 51.
[4] I. Muz, Inorg. Chim. Acta 2019, 495, 118950.
[5] C. Bannwarth, E. Caldeweyher, S. Ehlert, A. Hansen, P. Pracht, J. Seibert, S. Spicher, S. J. W. I. R. C. M. S. Grimme, Wiley Interdiscip. Rev.-Comput. Mol. Sci. 2020, 11, e01493.
[6] F. Neese, Wiley Interdiscip. Rev.-Comput. Mol. Sci. 2018, 8, e1327.
[7] T. Lu, Q. X. Chen, J. Comput. Chem. 2022, 43, 539555.
[8] T. Lu, F. W. Chen, J. Comput. Chem. 2012, 33, 580592.