Path B - Module 30: Geometrical Measurements#

Does your new disulfide bridge change the catalytic distance of PETase? In protein engineering, even a 0.1 nm shift can deactivate an enzyme.

In this module, you will learn to measure the exact geometry of your engineered biocatalyst to ensure its active site is still functional.

import molsysmt as msm
from molsysmt import systems

# Load your engineered PETase
molsys = msm.convert('pdb:6EQE', to_form='molsysmt.MolSys', selection='molecule_type=="protein"')
msm.build.add_missing_heavy_atoms(molsys)

1. Measuring the Catalytic Triad#

The catalytic triad of PETase consists of Ser160, Asp206, and His237. Let’s measure the distance between the Ser160 Oxygen and the His237 Nitrogen.

# Measure distance between specific atoms
distance = msm.get_distances(molsys, selection='group_id==160 and atom_name=="OG"', 
                             selection_2='group_id==237 and atom_name=="NE2"')

print(f"Catalytic distance (Ser-His): {distance}")

2. Monitoring the New Disulfide Bridge#

We mutated residues 238 and 289 to Cysteines. Let’s measure the distance between their sulfur atoms (SG) to see if they are close enough to form a bond (typically ~0.2 nm).

ss_dist = msm.get_distances(molsys, selection='group_id==238 and atom_name=="SG"', 
                            selection_2='group_id==289 and atom_name=="SG"')

print(f"Disulfide bridge distance: {ss_dist}")

3. All-vs-All Residue Distances#

You can generate a full distance matrix to see how the whole enzyme is organized spatially.

# Get distance matrix between the first 10 residues
dist_matrix = msm.get_distances(molsys, selection='group_index==[0:10]', center_of_selection=True)
print(f"Matrix shape: {dist_matrix.shape}")

🏆 Path B Challenge: The Precision Engineer#

  1. Calculate the distance between the C-alpha of residue 100 and residue 200.

  2. Find the Minimum Distance between the whole enzyme and its hydration shell (if you have water).

  3. Measure the Angle formed by the three C-alphas of the catalytic triad (160, 206, 237).

Geometry is the language of structure. In Module 31, we will analyze the Neighborhood of the plastic substrate in our active site.