Strychnine

Along the steps of this example workflow we will show how to:

  1. Generate different conformers of the molecule using CSEARCH

  2. Generate the inputs for the QM geometry optimization

  3. Fix error terminations and imaginary frequencies of the output files

  4. Calculation and analyze the NMR chemical shifts for the conformers generated.

  5. Use GoodVibes to calculate the Boltzmann distributions using Gibbs free energies at 298.15 K

Specifically, in this example we will calculate the NMR chemical shifts of the strychnine starting from the smiles representation of said molecule that we can see below.

SMILES

C1CN2CC3=CCO[C@H]4CC(=O)N5[C@H]6[C@H]4[C@H]3C[C@H]2[C@@]61C7=CC=CC=C75

Strychnine

Note

A jupyter notebook containing all the steps shown in this example can be found in the AQME repository in Github or in Figshare

Note

A video tutorial illustrating this example can be found in our youtube channel

Step 1: CSEARCH conformational sampling

python -m aqme --csearch --program rdkit --destination Strychnine_sdf_files --name Strychnine --smi "C1CN2CC3=CCO[C@H]4CC(=O)N5[C@H]6[C@H]4[C@H]3C[C@H]2[C@@]61C7=CC=CC=C75"

Step 2: Creating Gaussian input files for optimization and frequency with QPREP

python -m aqme --qprep --destination Strychnine_com_files --files "Strychnine_sdf_files/*.sdf" --program gaussian --qm_input "B3LYP/6-31+G(d,p) opt freq" --mem 24GB --nprocs 12

Step 3: Running Gaussian inputs for optimization and frequency calcs externally

Now that we have generated our gaussian input files (in the com_path location of Step 2) we need to run the gaussian calculations. If you do not know how to run the Gaussian calculations in your HPC please refer to your HPC manager.

As an example, for a single calculation in Gaussian 16 through the terminal we would run the following command on a Linux-based system:

g16 myfile.com

Step 4: QCORR analysis including isomerization filter

python -m aqme --qcorr --files "Strychnine_com_files/*.log" --freq_conv "opt=(calcfc,maxstep=5)" --isom_type com --isom_inputs Strychnine_com_files --nprocs 12 --mem 24GB

Step 5: Resubmission of unsuccessful calculations (if any) with suggestions from AQME

Now we need to run the generated COM files (in fixed_QM_inputs) with Gaussian like we did in Step 3.

After the calculations finish we check again the files using QCORR

python -m aqme --qcorr --files "Strychnine_com_files/failed/run_1/fixed_QM_inputs/*.log" --isom_type com --isom_inputs "Strychnine_com_files/failed/run_1/fixed_QM_inputs" --nprocs 12 --mem 24GB

Step 6: Creating Gaussian input files for NMR calcs with QPREP

python -m aqme --qprep --w_dir_main "Strychnine_com_files/success" --program gaussian --mem 24GB --nprocs 12 --suffix SP --destination Strychnine_sp_files --files "Strychnine_com_files/success/*.log" --qm_input "B3LYP/6-311+G(2d,p) scrf=(solvent=chloroform,smd) nmr=giao"

Step 7: Running Gaussian NMR calcs

Now we need to run the generated COM files (in sp_path) with Gaussian like we did in Step 3

After the calculations end, we create JSON files with QCORR to store the information from the resulting LOG files

python -m aqme --qcorr --files "Strychnine_sp_files/*.log"

Step 8: Obtaining Boltzmann weighted NMR shifts with QDESCP

python -m aqme --qdescp --program nmr --destination Strychnine_nmr_files --nmr_slope "[-1.0537, -1.0784]" --nmr_intercept "[181.7815,31.8723]" --nmr_experim Experimental_NMR_shifts.csv --files "Strychnine_sp_files/success/SP_calcs/json_files/*.json"

Step 9: Calculating conformer populations with GoodVibes

mkdir -p Strychine_GoodVibes-analysis
cp Strychnine_com_files/success/*.log Strychine_GoodVibes-analysis/
cp Strychnine_sp_files/success/SP_calcs/*.log Strychine_GoodVibes-analysis/
cd Strychine_GoodVibes-analysis
python -m goodvibes --xyz -c 1 *.log --boltz --spc SP
cd ..