Molecular orbital energies prediction with ML algorithms

Question

In the recent years, computational chemistry community has focused on Machine Learning algorithms to predict molecular properties. Unfortunately, many of the authors of such papers are not chemists, and hence, there are little explanation on chemical aspects of this type of works.

One well known problem is to predict different properties of QM9 dataset given their atom features. The properties include HOMO/LUMO orbital energies, atomization energies, etc. The inputs include type of heavy atoms in the molecule, type of their bonds, type of atom hybridization, etc. You can see a complete list in the following tables

The question is how the inputs are related to the outputs. For example, I understand that HOMO\LUMO energies are solutions of the electronic Schrödinger equation. But which one of the inputs features affects these? I appreciate it if someone can expand on which ones affect frontier molecular energies. Thanks!

Answer 1

As several comments have mentioned, interpreting a machine learning method can often be difficult. Outside the question of machine learning, I think your question centers around "what would I want to know to roughly predict HOMO / LUMO energies?"

Unfortunately QM9 isn't very diverse chemically, but if we think from a general qualitative molecular orbital picture (e.g., building up diatomic molecules), you want to know:

• Number of valence electrons (i.e., which orbitals are filled)
• Atom type (which tells you valence electrons and atomic orbital energies)
• Type of bond (e.g., single sigma bonds clearly will yield different MO energies than pi bonds)
• Conjugation - conjugated and aromatic systems will have different MO energies than plain sigma-bonded species
• Bond distances (from the Coulomb repulsion which encodes a distance $1/r$)

Given the above information, it's fairly easy to sketch out MO diagrams for $\ce{O2}$ or $\ce{HOH}$ so one can imagine that they're important for a machine learning algorithm too.

Now how do you know if they actually matter to the ML model?

One easy way is to drop one of the descriptors and retrain the model. Does it get worse? How much?

There are statistical techniques to give you some insight as well. For example, one can use LASSO to drop factors from the input representation that don't have much effect. You can also look at simple statistical correlation between input factors. I'd guess that "Atom Type" and "Atomic Number" are probably highly correlated with each other and only one is truly necessary.. but that's just a guess.