Path A - Module 36: Secondary Structure & Folds#

Proteins are defined by their folds. In the case of the Amyloid-Beta fibril, the transition from a random coil to a structured Beta-Sheet is the key pathological event.

In this module, you will learn to assign and quantify the secondary structure of your models using MolSysMT.

import molsysmt as msm
from molsysmt import systems

# Load the Amyloid-Beta fibril (2BEG)
fibril = msm.convert('pdb:2BEG', to_form='molsysmt.MolSys')

1. Assigning Secondary Structure#

MolSysMT identifies secondary structure elements (Helix, Sheet, Turn, Coil) for every residue. This usually requires external tools like DSSP, which MolSysMT handles for you.

# Get the secondary structure of the first chain
ss = msm.get(fibril, element='group', selection='chain_index==0', secondary_structure=True)

print(f"Secondary structure of the first 20 residues:\n{ss[:20]}")

2. Quantification#

Is our fibril actually a beta-sheet assembly? Let’s calculate the fraction of each structure type.

import numpy as np

unique, counts = np.unique(ss, return_counts=True)
stats = dict(zip(unique, counts))

total = sum(counts)
print("Secondary Structure Composition:")
for key in stats:
    print(f" - {key}: {100*stats[key]/total:.1f}%")

3. Dynamics of Folding#

Using the Villin trajectory, we can see how the secondary structure changes over time as the protein moves.

villin_traj = systems['chicken villin HP35']['traj_chicken_villin_HP35_solvated.dcd']
villin_topo = systems['chicken villin HP35']['chicken_villin_HP35_solvated.h5msm']
villin = [villin_topo, villin_traj]

# Get secondary structure for frames 0, 50, and 100
ss_time = msm.get(villin, element='group', selection='molecule_type=="protein"', 
                   structure_indices=[0, 50, 100], secondary_structure=True)

print(f"Number of frames analyzed: {len(ss_time)}")

🏆 Path A Challenge: The Structural Biologist#

  1. Calculate the secondary structure of your synthesized peptide (KLVFF) from Module 24.

  2. Compare the secondary structure of the peptide before and after you applied the beta-strand conformation in Module 27.

  3. Identify the residue indices that form the longest continuous Beta-Sheet in the 2BEG fibril.

Secondary structure defines the backbone stability. In Module 37, we will look at the specific chemical interactions that hold these sheets together: Hydrogen Bonds & Salt Bridges.