Molecular Dynamics and PDB Visualization System

A comprehensive molecular visualization and simulation platform built in Unreal Engine 5, featuring real-time molecular dynamics, binding affinity calculations, and interactive 3D visualization of protein structures.

Overview

This system provides a complete toolkit for molecular modeling and analysis, including:

• PDB file loading and visualization
• Real-time molecular dynamics simulation
• MM/GBSA binding affinity calculations
• Molecular interaction analysis (hydrogen bonds, salt bridges, pi-stacking, hydrophobic contacts)
• Interactive 3D camera controls
• Comprehensive UI for structure navigation and control

Core Components

PDBViewer

The central visualization engine that handles molecular structure display and interaction detection.

Key Features:

• Load and parse PDB files
• Render atoms and bonds with CPK coloring
• Calculate molecular interactions
• Manage multiple ligand structures
• Dynamic visibility control

Main Classes:

• APDBViewer - Primary viewer actor
• UPDBTreeNode - Hierarchical structure representation
• UPDBMoleculeNode - Individual molecule data

Molecular Dynamics Engine

High-performance O(N) molecular dynamics simulation with spatial hashing optimization.

Key Features:

• Multiple integration methods (Velocity Verlet, Leap-Frog, Runge-Kutta 4)
• Lennard-Jones and electrostatic forces
• Bond constraint enforcement (RATTLE algorithm)
• Temperature control via thermostat
• Real-time energy monitoring

Main Classes:

• AMolecularDynamics - Simulation engine
• FAtomState - Per-atom state tracking
• FBondConstraint - Bond constraint data

Parameters:

• Time step: 0.0001 - 0.01 fs
• Temperature: 0 - 1000 K
• Damping factor: 0.0 - 1.0
• Cutoff distance: Configurable for force calculations

MM/GBSA Binding Affinity Calculator

Molecular Mechanics / Generalized Born Surface Area method for calculating protein-ligand binding free energies.

Key Features:

• Complete energy decomposition (electrostatic, VDW, solvation, surface area)
• Structure quality assessment
• Clash detection and severity analysis
• Automatic charge assignment
• Ki/Kd dissociation constant calculation

Main Classes:

• AMMGBSA - Main calculation engine
• FBindingAffinityResult - Comprehensive results structure
• FEnergyComponents - Energy breakdown
• FStructureQuality - Quality assessment

Energy Components:

• Electrostatic interactions (Coulomb's law with distance-dependent dielectric)
• Van der Waals forces (Lennard-Jones 6-12 potential with soft-core)
• GB solvation (Generalized Born model)
• Nonpolar solvation (SASA-based)
• Conformational entropy penalty

Output:

• Binding free energy (ΔG in kcal/mol)
• Dissociation constant (Ki in nM)
• Affinity classification (Very Strong, Strong, Moderate, Weak)
• Detailed energy breakdown
• Structure quality report

Hydrogen Generator

Automated system for adding explicit hydrogens to molecular structures.

Key Features:

• Valence-aware hydrogen placement
• Support for sp3, sp2, and sp hybridization
• Geometry-specific positioning (tetrahedral, trigonal planar, linear)
• Bond order consideration

Main Classes:

• FHydrogenGenerator - Static hydrogen generation methods
• FAtomBondInfo - Bond connectivity tracking

Interaction Analysis

Comprehensive molecular interaction detection and visualization.

Interaction Types:

• Hydrogen bonds (distance and angle criteria)
• Salt bridges (charged residue pairs)
• Pi-stacking (aromatic ring interactions)
• Hydrophobic contacts

Main Classes:

• FMolecularInteraction - Interaction data structure
• Implemented in PDBViewer_Interactions.cpp

User Interface Widgets

MoleculeListWidget

List view of all loaded molecules with visibility controls and binding affinity display.

Features:

• Per-molecule visibility toggle
• One-click binding affinity calculation
• Color-coded affinity display
• Real-time updates

InteractionControlWidget

Control panel for molecular interaction analysis.

Features:

• Calculate interactions on demand
• Toggle interaction type visibility
• Protein-protein and protein-ligand filtering
• Interaction count statistics
• Detailed interaction list

MDControlWidget

Molecular dynamics simulation control panel.

Features:

• Start/stop/reset simulation
• Real-time energy monitoring
• Temperature control
• Integration method selection
• Force field parameter adjustment

PDBStructureWidget

Hierarchical structure browser with load/save functionality.

Features:

• Tree view of chains, residues, and atoms
• Load PDB files
• Save modified structures
• Clear current structure

Camera System

Advanced orbit camera with intuitive controls.

Controls:

• Right mouse button: Rotate around pivot
• Middle mouse button: Pan view
• Mouse wheel: Zoom in/out
• Spacebar: Fit molecule to screen

Main Classes:

• APDBCameraComponent - Camera controller

Technical Implementation

Performance Optimizations

Spatial Hashing:

• O(N) neighbor search for force calculations
• Dynamic cell size based on cutoff distance
• Efficient hash function for 3D grid

Verlet Neighbor Lists:

• Reduced force calculation frequency
• Skin distance for list validity
• Automatic rebuild when needed

Lazy Updates:

• On-demand interaction calculation
• Cached binding affinity results
• Conditional mesh updates

Physics Models

Force Fields:

• AMBER-compatible atom typing
• Partial charge assignment based on electronegativity
• Van der Waals radii from experimental data

Integration Methods:

• Velocity Verlet (default, 2nd order symplectic)
• Leap-Frog (energy-conserving, 2nd order)
• Runge-Kutta 4 (4th order accuracy, slower)

Constraints:

• RATTLE algorithm for bond length constraints
• Iterative satisfaction with configurable tolerance
• Maintains detailed balance for thermodynamics

Thermodynamics

Energy Conservation:

• Total energy monitoring (kinetic + potential)
• Configurable damping for stability
• Temperature scaling for NVT ensemble

Entropy Calculations:

• Base conformational entropy penalty
• Heavy atom count scaling
• Ligand-specific corrections

Usage Examples

Loading a Structure

APDBViewer* Viewer = GetWorld()->SpawnActor<APDBViewer>();
Viewer->LoadPDBFromPath("/Path/To/Structure.pdb");

Running Molecular Dynamics

AMolecularDynamics* MD = GetWorld()->SpawnActor<AMolecularDynamics>();
MD->InitializeFromViewer(Viewer);
MD->SetTemperature(300.0f);
MD->SetTimeStep(0.002f);
MD->StartSimulation();

Calculating Binding Affinity

AMMGBSA* Calculator = GetWorld()->SpawnActor<AMMGBSA>();
Calculator->InitializeFromViewer(Viewer);
FBindingAffinityResult Result = Calculator->CalculateBindingAffinity("LigandKey");
UE_LOG(LogTemp, Log, TEXT("ΔG = %.2f kcal/mol, Ki = %.2f nM"), 
    Result.DeltaG_Binding, Result.Ki_nM);

Analyzing Interactions

Viewer->CalculateAllInteractions(true, true); // Protein-protein and protein-ligand
TArray<FMolecularInteraction> HBonds = Viewer->GetInteractionsByType(EInteractionType::HydrogenBond);

Configuration

MM/GBSA Parameters

• Temperature: 298.15 K (physiological)
• Interior Dielectric: 10.0 (protein interior)
• Exterior Dielectric: 78.5 (water)
• Salt Concentration: 0.15 M (physiological)
• Charge Scaling: 0.95 (for unminimized structures)
• GB Scale Factor: 0.15 (empirical fit)

MD Parameters

• Time Step: 0.002 fs (default, adjustable)
• Cutoff Distance: 1200 Å (12 Å in real units)
• Neighbor List Skin: 200 Å (2 Å buffer)
• Constraint Iterations: 3 (RATTLE)

File Structure

├── PDBViewer.h/cpp                    # Main visualization engine
├── PDBViewer_Interactions.cpp         # Interaction detection
├── MolecularDynamics.h/cpp            # MD simulation engine
├── MMGBSA.h/cpp                       # Binding affinity calculator
├── HydrogenGenerator.h/cpp            # Hydrogen addition
├── PDBCameraComponent.cpp             # Camera controls
├── MoleculeListWidget.h/cpp           # Molecule list UI
├── MoleculeListEntry.h/cpp            # List entry widget
├── InteractionControlWidget.h/cpp     # Interaction UI
├── MDControlWidget.h/cpp              # MD control UI
├── PDBStructureWidget.h/cpp           # Structure browser UI
└── README.md                          # This file

Dependencies

• Unreal Engine 5.6+
• UMG (Unreal Motion Graphics) for UI
• Standard C++ library

Future Enhancements

• GPU acceleration for force calculations
• MMFF94 force field implementation
• Enhanced solvation models (Poisson-Boltzmann)
• Trajectory recording and playback
• Energy minimization algorithms (steepest descent, conjugate gradient)
• Multi-molecule docking
• Pharmacophore mapping
• QSAR model integration

License

This project is provided as-is for educational and research purposes.

References

• Molecular Mechanics: Leach, A.R. "Molecular Modelling: Principles and Applications"
• MM/GBSA: Genheden, S. & Ryde, U. "The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities"
• Generalized Born: Onufriev, A. et al. "Exploring protein native states and large-scale conformational changes"
• RATTLE Algorithm: Andersen, H.C. "Rattle: A 'velocity' version of the shake algorithm"

Contact

For questions, issues, or contributions, please contact:

Email: elassallemmer@gmail.com