Membrane Thickness & Protein Contact Remodeling

Overview and Methodology

What It Does

This tool analyzes both the structural and interactional dynamics of membrane–protein systems by computing:

1. Membrane Thickness:
   Average vertical (z-axis) distance between upper and lower lipid leaflets, calculated from headgroup atoms (e.g., phosphorus).

2. Protein–Lipid Contacts:
   The number of atomic contacts (within a user-defined cutoff) between a selected protein and surrounding lipid molecules.

3. Per-Residue Contact Changes:
   Tracks how contact frequency between specific residues and lipids increases or decreases over the trajectory.

How It Works

• Membrane Thickness:

  • Selects lipid atoms with a specified name (e.g., P).
  • Splits atoms into upper and lower leaflets using the median z-coordinate.
  • Calculates average z for each leaflet:

  $[ \text{Thickness} = \langle z_{\text{upper}} \rangle - \langle z_{\text{lower}} \rangle ]$

• Protein–Lipid Contacts:

  • Counts atom pairs between protein and lipid atoms within a distance threshold (default: 3 Å).
  • Aggregated over time to reveal contact trends.

• Residue-Level Tracking:

  • Measures change in contact counts from the start to the end of the simulation.
  • Top N residues showing gain or loss are plotted.

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Configuration and Inputs

Prerequisites

• Requires a loaded trajectory.

Key Configuration Options

• Selections:

  • protein_sel: Protein atom selection.
  • lipid_sel: Lipid atom selection.
  • headgroup_atom: Atom used to define leaflets (e.g., P in phospholipids).

• Contact Parameters:

  • contact_cutoff: Maximum distance (Å) for protein–lipid contact.
  • top_n_residues: Number of residues to highlight for gain/loss analysis.

• Simulation Settings:

  • time_total, step: Used to derive time axis for plots.

• Parallelization:

  • num_threads: Speed up frame-by-frame analysis.

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Output

Plots

• Membrane Thickness

  • Time-series of average lipid–lipid thickness.

• Protein–Lipid Contacts

  • Time-series of total contact counts between protein and lipid atoms.

• Residue-Level Bar Charts:

  • Top residues that gained the most lipid contacts.
  • Top residues that lost the most lipid contacts.

  All plots saved in:
  figures/{protein_name}_{lipid_name}_Membrane_Contacts.png

Data Export

• CSV Summary
  • Contains membrane thickness and contact count per frame:
    figures/{protein_name}_{lipid_name}_Analysis.csv

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Interpreting the Results

Membrane Thickness

• Stable Thickness:
  Suggests consistent bilayer integrity.

• Fluctuating Thickness:
  Could indicate protein-induced perturbation, lipid phase changes, or compression/stretching.

Total Contacts

• Decreasing Contacts:
  Protein may be detaching from the membrane or moving toward the bilayer center.

• Increasing Contacts:
  Suggests insertion, embedding, or spreading of protein into lipids.

Per-Residue Contact Trends

• Gainers:
  Residues becoming more exposed to or embedded in the bilayer.

• Losers:
  Residues losing lipid interactions, possibly due to rotation or displacement.

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Example Scenarios

Peripheral Membrane Protein Binding

• Observation: Steady increase in contacts with upper leaflet residues.
• Interpretation: Gradual insertion into the outer membrane surface.

Transmembrane Protein Drift

• Observation: Contact loss at extracellular loop residues, increase at intracellular helices.
• Interpretation: Protein shifts toward bilayer midplane or deeper insertion.

Lipid Rearrangement

• Observation: Large fluctuations in thickness; residues with sudden gain/loss.
• Interpretation: Lipid reorganization around a dynamic or rotating protein.

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Usage Tips

• Selection Strategy:

  • Use segid or resid restrictions to target specific chains or domains.

• Contact Threshold:

  • Adjust contact_cutoff (e.g., 3–5 Å) depending on lipid tail vs. headgroup resolution.

• Headgroup Atom:

  • Default is P, but can vary depending on the force field (e.g., O21, NC3).

• Protein Labeling:

  • Bar plot labels are auto-generated using OneLetterCode + ResidueID:SegID.

• Missing Data Handling:

  • Frames without valid selections are skipped; time series may have NaN.

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