Path B - Module 27: Conformational Engineering#

In the PETase enzyme, the residue Trp159 (Tryptophan) acts like a gatekeeper. In its “closed” conformation, it blocks the entrance of the plastic substrate. To simulate a reactive complex, we often need to rotate its sidechain to an “open” state.

In this module, you will learn to use set_dihedral_angles() to perform this specific engineering task.

import molsysmt as msm
from molsysmt import systems

# Load the PETase enzyme
petase = msm.convert('pdb:6EQE', to_form='molsysmt.MolSys', selection='molecule_type=="protein"')
msm.build.add_missing_hydrogens(petase)

1. Identifying the Gatekeeper#

Let’s find the residue ID 159 in our system and measure its current sidechain orientation (the \(\chi_1\) and \(\chi_2\) angles).

# Measure sidechain chi1 and chi2 for Trp159
chi1, chi2 = msm.get(petase, element='group', selection='group_id==159', chi1=True, chi2=True)

print(f"Trp159 Current Chi1: {chi1}")
print(f"Trp159 Current Chi2: {chi2}")

2. Opening the Gate#

Let’s rotate the \(\chi_1\) angle by adding 180 degrees to its current value. This will flip the large Tryptophan sidechain away from the active site cavity.

# Perform a relative shift of 180 degrees in chi1
msm.structure.shift_dihedral_angles(petase, selection='group_id==159', chi1='180.0 deg')

print("Trp159 has been rotated to the open conformation.")

3. Visual Confirmation#

Let’s visualize the active site to see if the cavity is now more accessible.

# View residues within 0.8 nm of the gatekeeper
msm.view(petase, selection='within 0.8 nm of group_id==159')

🏆 Path B Challenge: The Dihedral Master#

  1. Find the Catalytic Serine (Ser160).

  2. Measure its \(\phi\) and \(\psi\) backbone angles.

  3. Use msm.structure.set_dihedral_angles() to set its \(\chi_1\) angle to exactly -60.0 degrees (a common stable rotamer).

  4. Verify the new angle value using msm.get().

You have successfully manipulated the atomic orientation of your enzyme! In Module 28, we will learn how to use the MolSysBuilder API to build the plastic substrate itself from scratch.