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PULCHRA: High-Speed Full-Atom Protein Structure Reconstruction

PULCHRA (Protein Chain Reconstruction Algorithm) is a fast and robust computational method designed to reconstruct full-atom protein models from reduced representations. Developed by researchers at the Burnham Institute for Medical Research and the Georgia Institute of Technology, PULCHRA serves as a critical bridge between coarse-grained protein models and all-atom applications like molecular dynamics, protein-ligand docking, and structure-based function prediction.

By leveraging a hierarchy of structural optimizations, PULCHRA translates approximate protein folds into detailed atomic structures in a fraction of a second, while automatically regularizing distorted geometries to ensure physical plausibility.

Key Innovations: Fast and Flexible Chain Assembly

PULCHRA utilizes a modular reconstruction pipeline that can handle diverse input types, from α-carbon-only traces to side-chain centers of mass.

  • Multi-Step Reconstruction Pipeline: Features optional, independent steps including α-carbon optimization, backbone reconstruction, side-chain heavy atom placement, and hydrogen addition.

  • Geometric Regularization: Employs a steepest-descent minimization using a simple harmonic potential to correct unphysical α-carbon virtual bond distances and angles often found in cluster centroids.

  • Hydrogen Bond Optimization: Adjusts peptide bond orientations to maximize hydrogen bonding patterns in α-helices and β-sheets, using the validated DSSP energy formula.

  • Advanced Clash Mitigation: Iteratively searches rotamer libraries and rotates side chains around virtual bonds to eliminate over 95% of initial heavy-atom clashes while preserving natural packing.

  • Physical Plausibility Checks: Automatically detects and attempts to fix "punched" aromatic rings and improper chirality (D-amino acids) that would otherwise break molecular mechanics simulations.

Performance Benchmarks

PULCHRA consistently delivers reconstruction quality comparable to established methods while maintaining a significant advantage in computational speed.

Metric

PULCHRA Result

Key Finding

Reconstruction Speed

~0.8s per protein

Up to 36x faster than SCWRL on decoy sets.


All-Atom RMSD

0.97 Å

High precision when side-chain centers of mass are provided.


Backbone Precision

0.50 Å

Reconstructs backbone atoms with high accuracy from native traces.


Clash Resolution

> 95% removed

Successfully resolves atomic overlaps even in distorted structures.


Punched Ring Fixing

~99% success rate

Outperforms SCWRL and SCATD in generating physically valid decoys.


Scientific Breakthroughs in Model Building

Bridge Coarse-Grained and All-Atom Space

Reduced protein representations are essential for efficient conformational sampling. PULCHRA allows researchers to perform large-scale folding simulations and immediately convert the resulting ensembles into all-atom formats required for functional analysis or virtual ligand screening.

Robustness Against Distorted Data

PULCHRA was specifically designed to handle "real-world" predicted decoys that often exhibit serious geometric irregularities. In tests on 500 TASSER-generated decoys, it generated reasonable models even where traditional tools failed or produced non-physical arrangement errors like punched rings.

Repertoire and Trajectory Processing

The standalone executable is optimized for high-throughput tasks, including the processing of multi-model PDB files from molecular simulation trajectories and multi-chain quaternary structures.

PULCHRA on Tamarind Bio: High-Throughput Refinement

Tamarind Bio provides a managed, high-performance environment to deploy PULCHRA's reconstruction workflows, removing the need for local compilation or manual PDB manipulation.

  • No-Code Trajectory Analysis: Automatically process thousands of simulation snapshots to generate all-atom trajectories in minutes.

  • Scalable Model Refinement: Use PULCHRA as a fast preprocessing step before launching expensive molecular mechanics or docking campaigns on Tamarind’s secure cloud.

How to Use PULCHRA on Tamarind Bio

  1. Access the Platform: Log in to tamarind.bio and select the PULCHRA Reconstruction tool.

  2. Upload Structure: Provide a PDB file containing a reduced protein representation (e.g., α-carbon trace or side-chain centers).

  3. Configure Optimization: Choose to enable or disable specific routines like α-carbon regularization or backbone hydrogen bond optimization.

  4. Set Modeling Modes: Define treatment for multi-chain models, cis-prolines, or known chain breaks.

  5. Run Reconstruction: The platform executes the C-based algorithm to produce full-atom PDB files in milliseconds per structure.

  6. Evaluate Results: Analyze per-residue RMSD reports and DSSP hydrogen bond energy changes before exporting for downstream docking or dynamics.

Source

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