Path A - Module 39: Physicochemical Properties#

To finish your characterization, you need hard physical numbers. How much does your complex weigh? What is its net charge? And most importantly: how much surface area is buried when the peptide binds to the fibril?

In this module, you will learn to extract these physicochemical parameters using MolSysMT.

import molsysmt as msm
from molsysmt import systems

# Load our solvated complex
fibril = msm.convert('pdb:2BEG', to_form='molsysmt.MolSys')
peptide = msm.build.build_peptide('KLVFF')
molsys = msm.merge([fibril, peptide])

1. Mass and Charge#

Every Master needs to know the scale of their system. Is it a small peptide or a massive polymer?

# Calculate total mass and total charge of the whole system
mass = msm.physchem.get_mass(molsys)
charge = msm.physchem.get_charge(molsys)

print(f"Total Mass: {mass}")
print(f"Total Net Charge: {charge}")

2. Solvent Accessible Surface Area (SASA)#

SASA measures how much of the molecule is “visible” to the water molecules. It is a proxy for solubility and folding stability.

# Calculate SASA for the peptide alone
sasa_peptide = msm.physchem.get_sasa(molsys, selection='molecule_type=="peptide"')

print(f"Peptide SASA: {sasa_peptide}")

3. Interface Analysis: Buried Area#

This is the “Gold Standard” for binding analysis. The Buried Area is the surface area that is lost when two molecules come together. A higher buried area usually means a stronger binding.

# Calculate area buried between the peptide and the fibril
buried_area = msm.physchem.get_area_buried(molsys, selection='molecule_type=="peptide"', 
                                           selection_2='molecule_type=="protein"')

print(f"Total Buried Area: {buried_area}")

# You can also get the fraction of the peptide that is buried
fraction = msm.physchem.get_buried_fraction(molsys, selection='molecule_type=="peptide"', 
                                            selection_2='molecule_type=="protein"')

print(f"Fraction of peptide surface hidden in the complex: {fraction*100:.1f}%")

🏁 END OF PHASE 4: DATA ANALYST#

Congratulations! You have completed the scientific characterization of your Alzheimer’s model. You have measured:

  1. Distances and Angles.

  2. Neighborhoods and Contacts.

  3. Global Metrics (RG, RMSF, PCA).

  4. Secondary Structure.

  5. Hydrogen Bonds and Salt Bridges.

  6. Mass, Charge, and Buried Area.

Your model is perfectly understood. Now it is time to move from static analysis to dynamic physics. In Phase 5: The Physics Lab, we will prepare the system for real simulation in OpenMM.