Path A - Module 27: Conformational Engineering#

Biological function is determined by shape. In this module, you will learn to manipulate the internal degrees of freedom of your peptide: the Dihedral Angles.

By rotating these bonds, you can transition your therapeutic candidate from a random coil into a perfect beta-strand that can intercalate into the Alzheimer’s fibril.

import molsysmt as msm
from molsysmt import systems

# Synthesize a fresh KLVFF peptide for manipulation
peptide = msm.build.build_peptide('KLVFF')

1. Reading Current Angles#

First, we need to know the current state of our peptide. We will retrieve the \(\phi\) (phi) and \(\psi\) (psi) angles of the backbone.

# Get backbone dihedral angles
phi, psi = msm.get(peptide, element='group', phi=True, psi=True)

print(f"Current Phi angles: {phi}")
print(f"Current Psi angles: {psi}")

2. Imposing a New Shape with set_dihedral_angles()#

Let’s force the peptide into an extended (beta-strand) conformation. In a beta-strand, phi is usually around -135° and psi around +135°.

import numpy as np
deg = msm.pyunitwizard.unit('deg')

# Define target angles for all residues
n_groups = msm.get(peptide, element='system', n_groups=True)
target_phi = np.full(n_groups, -135.0) * deg
target_psi = np.full(n_groups, 135.0) * deg

# Apply the new conformation
msm.structure.set_dihedral_angles(peptide, phi=target_phi, psi=target_psi)

print("New beta-strand conformation imposed.")
msm.view(peptide)

3. Fine-tuning with shift_dihedral_angles()#

If you just want to rotate a specific bond a little bit (e.g., to resolve a clash or test a sidechain position), you can use shift to add an offset to the current value.

# Rotate the psi angle of the third residue by 45 degrees
msm.structure.shift_dihedral_angles(peptide, selection='group_index==2', psi='45.0 deg')

new_psi = msm.get(peptide, element='group', selection='group_index==2', psi=True)
print(f"Updated Psi for residue 2: {new_psi}")

🏆 Path A Challenge: The Helix-Maker#

  1. Take a fresh KLVFF peptide.

  2. Use msm.structure.set_dihedral_angles() to turn it into an alpha-helix. Hint: Alpha-helices have phi \(\approx\) -57° and psi \(\approx\) -47°.

  3. Use msm.view() to verify it looks like a spiral.

  4. Measure the distance between the first and last C-alpha atoms.

You are now a master of molecular shape! In Module 28, we will learn how to build complex systems from the ground up using the MolSysBuilder API.