Path B - Module 38: Advanced H-Bond Algorithms#

In industrial Biocatalysis, water is not just a solvent; it is often a co-reactant or a structural stabilizer. To study the hydration of the PETase active site, a general H-bond criterion might be too loose.

In this module, you will learn to use specialized algorithms like Buch and Luzar-Chandler to refine your interaction analysis.

import molsysmt as msm
from molsysmt import systems

# Load our solvated complex
petase = msm.convert('pdb:6EQE', to_form='molsysmt.MolSys', selection='molecule_type=="protein"')
msm.build.add_missing_hydrogens(petase, pH=8.0)

bhet = msm.convert('C1=CC(=CC=C1C(=O)OCCO)C(=O)OCCO', from_form='string:smiles', to_form='molsysmt.MolSys')
msm.build.add_missing_hydrogens(bhet)

molsys = msm.merge([petase, bhet])

1. The Buch Criterion#

The Buch algorithm is particularly useful for identifying H-bonds in aqueous environments where geometry needs to be strictly defined. Let’s see how many H-bonds it detects in the active site.

# Find H-bonds using the Buch criterion
buch_hbonds = msm.hbonds.get_buch_hbonds(molsys, selection='molecule_type=="small molecule"', 
                                        selection_2='molecule_type=="protein"')

print(f"Buch H-bonds: {len(buch_hbonds)}")

2. Refined Donor/Acceptor Rules#

Industrial enzymes may have non-standard groups. You can tell MolSysMT exactly which atoms should be considered as potential donors or acceptors.

# Find all donors in the protein but EXCLUDE the Histidine 237 (to test a hypothesis)
donors = msm.hbonds.get_donor_atoms(molsys, selection='molecule_type=="protein"', 
                                    exclusion_rules=['group_id==237'])

print(f"Total custom donors: {len(donors)}")

3. Luzar-Chandler Analysis#

Let’s compare the results with the Luzar-Chandler algorithm, which uses a more standard geometric cutoff (3.5 Å for distance, 30° for angle).

# Find H-bonds using Luzar-Chandler
lc_hbonds = msm.hbonds.get_luzard_chandler_hbonds(molsys, selection='molecule_type=="small molecule"', 
                                                 selection_2='molecule_type=="protein"')

print(f"Luzar-Chandler H-bonds: {len(lc_hbonds)}")

🏆 Path B Challenge: The Hydration Analyst#

  1. Calculate the H-bonds between the BHET substrate and the Solvent (water) molecules.

  2. Which algorithm (Buch vs Luzar-Chandler) gives a more conservative (smaller) number of bonds?

  3. Identify the most frequent acceptor atom in the enzyme’s active site.

You have completed the interaction characterization! In Module 39, we will finish the Analyst phase by extracting the Physicochemical Properties of your mutant enzyme.