Workshop A-SIDE

Step-by-step (Atomistica.online 2025)

Step 1. Get the structure

Download the caffeine .xyz file above.

Step 2. Open the calculator

Once you have downloaded the molecular structure, open the main page of Atomistica Online 2025. On the left-hand menu, you will see several categories of available tools. Under the category “Calculators,” find and click on the tool named “xTB & g-xTB.”

This tool enables you to perform different types of atomistic calculations using Grimme’s family of GFN-based methods (GFN0, GFN1, GFN2, GFN-FF, and g-xTB). These methods belong to the class of semiempirical atomistic approaches, which balance accuracy and speed. They are ideal for beginners because they require only the molecular structure as input, no complex setup is needed.

After selecting “xTB & g-xTB,” the main calculation interface will open, where you can upload your molecule and adjust calculation settings.

Step 3. Import the molecule

Click “Upload .xyz or .pdb file” and select caffeine.xyz.

Step 4. General settings

Once the molecular structure of caffeine is uploaded, you will see several sections in the interface. The first one is called “General Settings.”

In this section, you can define what kind of calculation will be performed and which computational method will be used.
For the purpose of this exercise, you do not need to change any of the default values. Simply keep everything as it is, this will ensure that your calculation runs smoothly and quickly.

By default, the Task is set to “Energy”, and the Method is set to “GFN2-xTB.” This combination means that xTB program in the background will perform a single-point energy calculation, which calculates the total electronic energy of the molecule at the given geometry (without changing atomic positions).

The GFN2-xTB method, developed by Prof. Stefan Grimme and co-workers, is part of the xTB family of semiempirical quantum-chemical methods. It provides a reliable estimate of molecular energies and structures at a fraction of the cost of more advanced DFT or ab initio approaches. Once you have confirmed these settings, you are ready to start your first calculation.

Step 5. Run

Click RUN XTB. The calculation will finish within a few moments, except when you later choose g-xTB, which is a slightly more computationally demanding method than the GFN family of methods. When you choose g-xTB, the calculation will take around 15 seconds to finish.

Step 6. Reading and Downloading the Output File

Once the calculation is completed, the text area labeled “Output file” will automatically display the content of the output file generated by the xTB calculation.
This file contains all numerical data, parameters, and messages directly printed by the xTB program during the calculation.

You can carefully scroll through this text area to inspect the results. Near the end of the file, you will find a line containing the key information — the “TOTAL ENERGY” of the molecule. This value represents the total electronic energy of the caffeine molecule calculated with the selected method.

If you wish to keep a copy of the full output file for later analysis, you can simply click on the “Download output” button. This will download the output file to your computer.

Finally, copy the energy value and its units and record them in your table (CSV template provided). After repeating the same steps for each method, you will have a complete overview of how total energies differ across computational approaches.

Step 7. Compare multiple methods

Go back to Step 4, and under the General Settings section, change the method by clicking on the “Select method” dropdown menu.
Instead of “GFN2-xTB,” choose “GFN1-xTB.”

Repeat Steps 4 through 6 and record the total energy for this method.
Then continue the same procedure for the remaining methods: GFN0-xTB, GFN-FF, and g-xTB.

When you finish, you should have a table in which the energy of the caffeine molecule is calculated using five different methods, meaning your table should contain five energy values in total.

Step 8. Analysis and Discussion

Now that you have obtained the total energy of the caffeine molecule using all five methods, it is time to analyze your results.

Carefully compare the energy values listed in your table. You will notice that the numbers are not identical, even though the same molecular structure was used in every calculation. This difference arises because each computational method, GFN0-xTB, GFN1-xTB, GFN2-xTB, GFN-FF, and g-xTB, uses a different set of approximations, parameterizations, and physical models to describe the molecular system.

Methods such as GFN0/1/2-xTB are semiempirical atomistic approaches that include electronic structure information, while GFN-FF is a force-field method based purely on classical parameters. The g-xTB method is more sophisticated and computationally demanding, offering improved accuracy by incorporating advanced corrections.

In summary, each method estimates molecular energy differently, which is why the resulting numbers vary.
This step helps you understand one of the fundamental concepts in computational chemistry, that the choice of method directly influences the numerical results and their level of accuracy.