Path B - Module 33: Ensemble Descriptors (Global Metrics)#

Did your engineered mutations make the PETase more compact? Global descriptors allow you to summarize the overall physical state of your enzyme.

In this module, you will learn to calculate the Radius of Gyration and identify flexible regions using RMSF.

import molsysmt as msm
from molsysmt import systems

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

1. Radius of Gyration (RG)#

RG is a proxy for how tightly packed the protein is. For industrial enzymes, maintaining a compact core is usually correlated with higher thermal stability.

# Measure the global RG of the enzyme
rg = msm.structure.get_radius_of_gyration(molsys)
print(f"PETase Radius of Gyration: {rg}")

2. Physical Center of Mass#

Knowing the center of mass is essential to center your molecule in the box before simulation.

# Calculate the mass-weighted center
com = msm.structure.get_center(molsys, weights='masses')
print(f"Center of Mass: {com}")

3. Fluctuations: RMSF#

Which parts of the PETase are the most “vibrational”? Regios with high RMSF are the best candidates for further mutations (e.g., adding more disulfide bridges).

# Using the Villin trajectory as a demo for RMSF calculation
villin_traj = systems['chicken villin HP35']['traj_chicken_villin_HP35_solvated.dcd']
villin_topo = systems['chicken villin HP35']['chicken_villin_HP35_solvated.h5msm']

rmsf = msm.structure.get_rmsf([villin_topo, villin_traj])
print(f"Average RMSF of the demo system: {rmsf.mean()}")

🏆 Path B Challenge: The Compacity Judge#

  1. Calculate the Radius of Gyration for each frame of a trajectory.

  2. Find the Standard Deviation of the RG to see if the enzyme’s size is fluctuating significantly.

  3. Use msm.structure.get_center() on the catalytic triad atoms only. Is it near the global center of mass?

Global descriptors summarize the physics of your system. In Module 34, we will learn to Superimpose structures to see how your mutant differs from the wild-type.