Protein–Lipid Contact Time Series

Overview and Methodology

What It Does

This script detects and quantifies contacts between protein residues and lipid atoms over the course of a molecular dynamics (MD) simulation. It outputs a time series contact matrix where each row corresponds to a protein residue and each column represents a frame in the trajectory. A contact is registered when any atom of a protein residue is within a user-defined cutoff distance from any lipid atom.

How It Works

• Objective: Identify residues that are in contact with lipids over time and map out these interactions as a binary matrix.
• Process:
  • For each trajectory frame:
    • Select protein residues and lipids that are spatially close based on a distance cutoff.
    • Optionally limit contact detection to specific lipid atoms (e.g., headgroups).
    • Calculate distance matrices between protein and lipid atoms.
    • Assign a contact (1) if any atom in a residue falls within the cutoff distance.
  • Parallel processing is available for speed-up across frames.
  • The resulting data is a residue-by-time contact matrix, which can be used for further analysis or visualization.

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Configuration and Inputs

Prerequisites

• Requires a loaded trajectory.

Key Configuration Options

• Selections:

  • protein_sel: Atom selection string for the protein (e.g., 'segid VSD').
  • protein_name: Label used in the output file naming and title.
  • lipid_sel: Atom selection string for lipids (e.g., 'segid MEMB').
  • lipid_name: Label used in output and title.
  • lipid_atom: Optional filter for lipid atoms to include in distance computation (e.g., 'P').

• Contact Parameters:

  • contact_cutoff: Distance threshold (Å) to define a contact between protein and lipid atoms.

• Timing and Trajectory Control:

  • time_total: Duration of the trajectory in physical units (used for x-axis labeling).
  • begin_frame, end_frame, step: Frame range and sampling interval.
  • show_progress: Enables progress updates during processing.

• Parallelization:

  • num_threads: Number of CPU threads for multiprocessing. Set -1 to use all available cores.

• Filtering and Output Control:

  • ts_min_fraction: Minimum fraction of trajectory time a residue must contact lipids to be included in the output.
  • Frame-by-frame residue labels are dynamically assigned based on the active selection and are auto-matched.

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Output

• DataFrame:

  • Rows: Protein residue labels in the format X123:SEGID, where X is the one-letter residue code.
  • Columns: Time points corresponding to trajectory frames.
  • Values: 1 if contact occurs, 0 otherwise.

• Saved Files:

  • CSV: Binary contact matrix saved to figures/{protein_name}_{lipid_name}_Contact_Time_Series.csv.
  • PNG: (Optional if plotting is included) Heatmap figure saved to figures/{protein_name}_{lipid_name}_Contact_Time_Series.png.

• Console Output:

  • Frame-by-frame debug summaries including:
    • Number of lipid residues near protein.
    • Count of contacting residues.
    • z-axis ranges of protein and lipid atoms.
    • Error messages for frames with missing atoms or contacts.

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Interpreting the Results

• Contact Matrix:

  • Each 1 indicates that a residue was in contact with lipids during a specific frame.
  • Absence of contacts (all 0s for a residue) means it was either too distant or excluded due to filtering.
  • Residues present in fewer frames than ts_min_fraction are omitted to improve clarity.

• Debug Info:

  • Useful for diagnosing issues such as missing selections, incorrect atom names, or overly strict cutoffs.
  • z-axis range information can be used to assess membrane embedding depth or drift during simulation.

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Example Scenarios

Membrane-Binding Domain Analysis

• Observation: Peripheral residues show sporadic contact with the lipid bilayer.
• Interpretation: Suggests transient membrane binding or surface association.

Transmembrane Helix Stability

• Observation: Stable contacts across all frames for central helices.
• Interpretation: Indicative of consistent embedding within the membrane core.

Drug-Induced Reorganization

• Observation: Change in contact pattern after specific simulation time point.
• Interpretation: Potential effect of bound compound altering protein-lipid interaction network.

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Usage Tips

• Atom Filtering:

  • Use lipid_atom='P' or similar to restrict contact detection to lipid headgroups for biologically relevant interactions.

• Performance:

  • Increase num_threads for long trajectories to speed up analysis.
  • Lower ts_min_fraction to retain more residues, but at the cost of visual clarity.

• Edge Cases:

  • No detected contacts may indicate overly strict cutoff or incorrect selections.
  • Use debug outputs to verify spatial proximity and atom selections.

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