Changelog

All notable changes to this project will be documented in this file.

The format is based on Keep a Changelog, and this project adheres to Semantic Versioning.

[1.37.0] - 2026-05-14

Added

Modern Formats Support: Native support for mmCIF (PDBx) and BinaryCIF (BCIF) output via the --format flag.
Massive Protein Support: Ability to generate structures with over 99,999 atoms and 62 chains using the CIF format.
BinaryCIF Export: High-performance binary format for AI pipelines and web-based visualization (Mol*).
Interactive Tutorials: Restored and improved interactive Jupyter Notebooks for NeRF geometry and protein quality assessment.
ASCII-Only Standard: Package-wide migration to ASCII-safe strings to prevent encoding crashes in restricted terminal environments.

Fixed

Core Performance: Vectorized B-factor and occupancy calculations using NumPy, resulting in >10x speedup for large protein generation.
Validator Optimization: Significant performance improvements to PDBValidator for large structures.
Reproducibility: Restored strict seed propagation for all generation modes and formats.

[1.36.0] - 2026-05-04

Added

Enhanced Prompt Transparency: The CLI now explicitly logs interpreted command-line arguments when using the --prompt interface, providing full visibility into how the LLM maps natural language to biophysical parameters.
Intelligent CLI Logging: Implemented a custom CLIFormatter that keeps standard output clean while explicitly labeling WARNING: and ERROR: messages for improved diagnostic visibility.
Robust Prompt Documentation: Added a "Tips for Reliable Generation" section to the Prompt-to-Protein guide, covering SLM hallucination management and clinical phrasing best practices.
Explicit GPU Control: New --platform and --precision flags for OpenMM-driven energy minimization, allowing users to force CUDA, Metal, or OpenCL platforms and choose between single, mixed, or double precision for optimized performance.
Physics Progress Tracking: Integrated LoggingMinimizationReporter to provide real-time energy convergence feedback during minimization at the DEBUG level.
Hardware Acceleration Benchmark: New scripts/benchmark_hardware.py utility to quantify performance gains across different compute platforms (CPU vs GPU).

Fixed

Metal Coordination Realism: Refactored the Zinc Finger detection logic to require ligands from 4 unique residues (chain + residue ID mapping). This eliminates false-positive coordination sites caused by "double-counting" multiple atoms (e.g., His NE2/ND1) from the same residue.
CLI Logging Stream: Standardized logging output to stderr to ensure compatibility with shell piping and automated test suites.
Memory Management: Implemented caching for functional OpenMM platforms and improved cleanup in simulate_trajectory to resolve intermittent memory leaks and redundant initialization overhead.
Dependency Stability: Explicitly excluded buggy OpenMM versions (8.5.0, 8.5.1) to protect against known upstream memory leaks.

[1.35.0] - 2026-05-02

Added

Circular Dichroism (CD) Simulator: New synth_pdb.cd_simulator module for generating synthetic Far-UV CD spectra from 3D structures.
Interactive CD Lab tutorial in examples/interactive_tutorials/.

[1.34.2] - 2026-04-28

Fixed

BMRB Validation Pipeline: Updated PDBValidationAPI to use the unified PDBe v2 API, resolving 404 errors during metadata retrieval. Added a compatibility shim to maintain support for legacy field names in existing tutorials.

[1.34.1] - 2026-04-27

Added

Updated Gallery Images: Enhanced visual snapshots in the examples gallery for better structural clarity.
Version Synchronization: Unified version metadata across documentation header, PyPI badges, citation guides, and Streamlit app.

[1.34.0] - 2026-04-27

Added

High-Fidelity SAXS Visualization: Integrated Standard, Kratky, and Guinier plots into the CLI and core library for biophysical assessment of protein folding and dimensions.
Scientific Rigor Suite: New automated validation against peer-reviewed benchmarks (Waasmaier & Kirfel 1995 for form factors; Kratky & Porod 1949 for folding signatures).
Multi-Modal Dataset Factory: New scripts/build_multimodal_dataset.py for high-throughput generation of synchronized PDB, MRC, SAXS, and NMR data for AI training.
Robust Sequence Parsing: Support for 4-letter D-amino acid shorthands (DALA, dALA) and Selenocysteine (SEC/U).
Interactive Cryo-EM & SAXS Lab: New tutorial showcasing ensemble-averaged density and scattering simulation.
Embedded Gallery Visuals: Added snapshots for all major structural types in the examples documentation.

Fixed

CLI Robustness: Fixed docking mode to support on-the-fly generation from sequence strings.
PDB Compliance: Updated atom formatting for 2-character elements (like Selenium) to meet rigorous PDB standards.
Browser Automation: Mocked webbrowser in test suites to prevent unintended popup windows during CI runs.

[1.33.0] - 2026-04-26

Added

Comprehensive API Documentation: 11 new modules fully documented including cryo_em, saxs, docking, cofactors, and special_chemistry.
New Interactive Tutorials:
- cryo_em_saxs_lab: Visualizing resolution and conformational heterogeneity.
- bmrb_validation: Programmatic validation against experimental NMR data.
Multimodal Science Guide: New guide explaining integrated scientific workflows.
Enhanced Ensemble Support: Added PeptideGenerator.generate_ensemble() for high-performance vectorized generation.

Fixed

Memory Leaks: Resolved critical memory leaks in OpenMM physics engine and BatchedGenerator template caching.
Tutorial Modernization: Updated gfp_molecular_forge and neural_nmr_pipeline to use the latest APIs.
Test Integrity: Standardized documentation integrity tests and added coverage for new features.

[1.32.0] - 2026-04-24

Added

AI Mode: Structure Clustering: Implemented RMSD-based clustering for protein conformational ensembles.
- New CLI flag: --mode ai --ai-op cluster
- Supports --input-pattern (glob) and --n-clusters.
- Automatically superimposes structures to a reference before clustering.
- Exports representative "medoid" structures for each cluster to a user-defined directory.
Improved Testing: Added tests/test_clustering.py for full-workflow CLI validation.

[1.31.0] - 2026-04-24

Added

GNN Quality Filter Calibration: New sensitivity suite in tests/test_gnn_calibration.py validating that the GNN model correctly responds to coordinate noise, steric clashes and backbone distortions.
Comprehensive Testing Suite: Added massive coverage expansion for evolution kernels, packing algorithms, scoring functions and geometric edge cases (RMSD/superposition).
Non-Standard Residue Support: Enhanced chemical shift and RDC predictors to gracefully handle non-standard residues (PTMs, D-amino acids) while maintaining pedagogical documentation density.
Local Notebook Validation: Added scripts and environment setups (scripts/setup_colab_venv.sh, test_notebooks_local.sh) to verify tutorial notebooks in a production-like local environment.

Fixed

D-Amino Acid Stereochemistry: Corrected critical bugs in D-amino acid generation, ensuring biophysically accurate backbone mirroring and side-chain placement.
Chiral NMR Inversion: Implemented a dual-pass coordinate inversion strategy for D-amino acid chemical shifts, ensuring predicted values respect chiral symmetry.
Physics Engine Stability: Resolved memory leaks and ensured consistent implicit solvent behavior across the EnergyMinimizer pipeline.
Generator Parity: Guaranteed 1:1 structural parity between BatchedGenerator and the standard PeptideGenerator.
CLI Robustness: Strengthened argument validation in main.py and added regression tests for CLI flag collisions.
PTM Template Mismatch: Fixed an issue where PTM residue templates (SEP/TPO/PTR) were incorrectly handled during physics preprocessing.

Changed

Documentation Density: Significantly increased inline "Educational Notes" in coupling.py, msa.py and physics.py.
CI Modernization: Added Numpy 2.3.5 to the automated test matrix; refactored the J-Coupling shim for structural TDD.

[1.30.0] - 2026-04-22

Added

New Documentation Pages:
docs/api/rdc.md: Full API reference for synth_pdb.rdc — Saupe-matrix RDC back-calculation, Q-factor interpretation table, alignment media comparison and complete workflow example.
docs/api/ensemble.md: Full API reference for synth_pdb.ensemble — DAOPCalculator, EnsembleStatistics, and QualityAssessment with Tejero 2013 quality thresholds.
docs/science/ensemble-analysis.md: Science background page explaining DAOP circular statistics, coordinate RMSD/RMSF, medoid selection, and IDP ensemble caveats.
Documentation Expansions:
docs/getting-started/first-structure.md: Rewrote stub into a full 5-step walkthrough (generate → visualise → validate → minimise → Python API).
docs/physics.md: Added simulate_trajectory() section with Kabsch-aligned RMSF example and autodoc integration.
docs/nmr.md: Expanded from 26-line stub to comprehensive coverage of all NMR observables (NOE/NEF, chemical shifts, relaxation, RPF scores, RDCs, J-couplings).
README Additions:
Added 6 new feature blocks: RDC module, NMR Ensemble Analysis, MSA Co-Evolution, PLM Embeddings, GNN Quality Scorer, and Engh & Huber / Top2018 validation details.
Updated project structure tree to reflect current 30+ module layout including geometry/, ensemble/, quality/gnn/, rdc.py, msa.py, plm.py.
Added 20 new glossary entries (BMRB, DAOP, DCA, Engh & Huber, ESM-2/PLM, GNN, IDR/IDP, Kauzmann, Magic Step, MCMC, Orientogram, pLDDT, Potts Model, PPII, PRE, Q-factor, RDC, RMSF, Saupe Matrix, Top2018).
Added 11 new references (Engh & Huber 1991, Hyberts 1992, Tejero 2013, Tjandra & Bax 1997, Saupe 1968, Morcos 2011, Lin 2023, Jumper 2021, Ruff & Pappu 2021, Clore & Iwahara 2009, Cornilescu 1998).

Fixed

Docs site badges: Replaced broken Open in Colab badge (pointed to non-existent demo.ipynb) with correct link to examples/interactive_tutorials/virtual_nmr_spectrometer.ipynb.
PyPI badge: Replaced unreliable badge.fury.io endpoint with live shields.io/pypi/v badge.
mkdocs.yml: Added api/rdc.md and api/ensemble.md to the API Reference nav; added science/ensemble-analysis.md to the Scientific Background nav.

[1.29.0] - 2026-04-20

Added

Aggressive Scientific Validation Framework: Implemented a comprehensive, evidence-based quality filter in PDBValidator that proactively defends generated models using peer-reviewed biophysical standards.
Engh & Huber Z-Scores: Integrated backbone geometry validation against the landmark Engh & Huber (1991) standard deviations for bond lengths and angles.
Dunbrack Rotamer Quality: Added sidechain packaging assessment based on the Dunbrack Rotamer Library, ensuring models follow natural PDB conformational probabilities.
SASA-based Burial Validation: Implemented calculate_residue_sasa() using the Shrake-Rupley algorithm (via biotite) and a "Burial Ratio" metric to verify hydrophobic core formation (Kauzmann 1959).
Modern Geometric Standards: Upgraded Ramachandran validation logic to align with the high-resolution Top2018 dataset (~15,000 chains).
Structural Integrity Report: New get_quality_report() method providing a multi-layered defense (Geometry + Physics + Biophysics) for structural plausibility.
NMR Integrations: New validation tests against mirror-image Protein G (BMRB 36464) and AI-refined Influenza NS1B-CTD (BMRB 51544).

Fixed

Backbone Superimposition: Corrected a critical regression where 4-atom superimposition caused backbone distortions. Restored stable 3-atom transformation (N, CA, C) for consistent global frame orientation.
D-Amino Acid Chirality: Fixed torsion negation logic to correctly handle mirror-image proteins via sidechain reflection while maintaining standard L-conformation backbone traces.
CI/CD Cleanup: Resolved numerous mypy and ruff issues across the source package; implemented warning filters to suppress external library noise (e.g., biotite deprecations).

[1.28.0] - 2026-04-04

Added

New Ensemble Module (synth_pdb.ensemble): A new subpackage housing NMR ensemble analysis algorithms, extracted from pdbstat-python and elevated to a general-purpose, scientifically validated library.
DAOPCalculator (synth_pdb.ensemble.daop): Implements the circular order-parameter formula from Hyberts et al. (1992) Protein Science 1:736 for quantifying dihedral angle consistency across an NMR ensemble. Includes calculate_order_parameter, find_well_defined_residues (PDBStat S(φ)+S(ψ) ≥ 1.8 convention), and calculate_backbone_daop.
EnsembleStatistics (synth_pdb.ensemble.statistics): Typed dataclass replacing plain Dict[str, float] for ensemble quality metrics (pairwise RMSD, RMSF, medoid, well-defined residues) with precision and overall_quality computed properties and to_dict/from_dict round-trips. Quality thresholds from Tejero et al. (2013) J Biomol NMR 56:337.
QualityAssessment (synth_pdb.ensemble.statistics): Lightweight typed dataclass for the precision/overall-quality assessment pair.

[1.27.0] - 2026-03-30

Added

New Geometry Module (synth_pdb.geometry): Modernized core protein geometry logic based upon pdbstat-python, including symmetry-aware RMSD calculation and rigid-body superposition.
Improved J-Coupling Prediction: Updated tests/test_coupling.py to support NaN key exclusions in the latest synth-nmr predictor.
Extensive Geometry Testing: Added edge-case kernels tests for RMSD, dihedral angles and Kabsch superposition.

Fixed

Geometric Strain Formula: Corrected calculation of omega dihedral deviation from 180° for consistent residue strain reporting.
Generator Robustness: Resolved systemic TypeError regressions caused by pytest-cov environment interference with numpy._NoValueType.

Changed

Dependency Update: Bumped synth-nmr dependency to >=0.9.0 for improved physical validation and J-coupling support.
CI/CD Stabilization: Hard-pinned documentation dependencies (mkdocstrings, mkdocstrings-python, and pygments) to ensure build site reproducibility and resolve NoneType errors in the MkDocs pipeline.

[1.26.0] - 2026-03-29

Added

MSA Modernization: Completely overhauled synth_pdb.msa to simulate biologically grounded evolutionary constraints.
Added \(O(1)\) Delta-Energy evaluation (calculate_delta_energy) yielding a ~500x acceleration in MSA generation via Metropolis-Hastings sampling.
Implemented the "Magic Step" coupled mutations allowing the MCMC simulation to simultaneously mutate contacting residues (defaults to 20% proposal rate).
Added SASA Selective Pressure via rel_sasa enforcing geometric isolation of the hydrophobic core.
Expanded Potts Model J_ij coupling to factor in Electrostatic Salt Bridges (rewards) and Repulsions (penalties).
Expanded Physics Testing Suite: Added dedicated test_physics_expansion.py boosting the physics engine coverage layout (fixing systemic segmentation faults driven by template caching errors).
Formalized Docstrings: Embedded the biological rationale of Hydrophobic Collapse and "Magic Steps" directly into the algorithm source code as dense "Educational Notes" and created a dedicated MkDocs "Co-Evolution" background page.

Fixed

Type Checking Strictness: Fixed an unhandled mypy typing coercion causing the energy matrices to leak generalized Any objects.

[1.25.0] - 2026-03-10

Changed

Dependency Update: Required synth-nmr>=0.8.0 to incorporate the latest NMR simulation engine improvements and physical validator updates.

[1.24.0] - 2026-03-08

Added

Synthetic MSA Generation with Co-Evolution (synth_pdb/msa.py): New generative workflow simulating Markov Chain Monte Carlo (MCMC) evolution over a 3D structural Potts Model, enabling zero-shot generation of deep multiple sequence alignments to test DCA/AlphaFold inputs.
MSA Mutual Information Tutorial (examples/interactive_tutorials/coevolution_msa_factory.ipynb): New interactive Jupyter notebook visually demonstrating how the physics-based MCMC sampler enforces co-evolution signals that recover the 3D contact map.
High-Density Physics Documentation Suite: Massively expanded the inline educational docstrings across synth_pdb/physics.py (>60% line density), exposing the physical rationale behind NVT Langevin dynamics, Amber forcefields, implicit solvents, and metadata restoration strategies.

[1.23.0] - 2026-03-07

Added

IDP Conformational Ensembles Tutorial (examples/interactive_tutorials/idp_ensemble_validation.ipynb): New interactive notebook validating synthetic IDP ensembles mathematically and visually against \(1/r^6\) Paramagnetic Relaxation Enhancement (PRE) NMR phenomena.
AlphaFold pLDDT vs NMR S² Tutorial (examples/interactive_tutorials/alphafold_vs_nmr_dynamics.ipynb): New interactive notebook modeling an unstructured loop to demonstrate the inverse correlation between static AI prediction confidence (pLDDT) and physical NMR flexibility.
IDP Theoretical Physics Documentation (docs/science/idp-dynamics.md): Added comprehensive biophysical theory documentation explaining how the BatchedGenerator successfully handles intrinsically disordered regions compared to rigid crystalline tools.

Fixed

Py3Dmol Widget Crash on Local Jupyter: Replaced IPyWidgets HBox layout with Py3Dmol's native viewergrid=(1,2) API across tutorials. This stops localized browser javascript injection blocks from breaking dual-viewer structures (fixing "3Dmol.js failed to load" spam).
GitHub Actions Formatting CI: Ran ruff check --fix . across the codebase, fixing un-sorted imports and line-length breakages introduced by physics.py trajectory logging features, restoring a completely 'green' test.yml CI workflow.

[1.22.0] - 2026-03-05

Added

Residual Dipolar Coupling (RDC) module (synth_pdb/rdc.py): New calculate_rdcs() function implementing the Saupe-matrix formalism for computing backbone N–H RDCs given an alignment tensor defined by axial component Da and rhombicity R.
RDC tutorial notebook (examples/interactive_tutorials/rdc_alignment_explorer.ipynb): Standalone Colab-compatible notebook demonstrating RDC calculation, Q-factor validation against published ubiquitin data (1D3Z), and interactive alignment-tensor exploration.
Virtual NMR Spectrometer — RDC section (virtual_nmr_spectrometer.ipynb cells 13–14): Interactive RDC fingerprint panel with ipywidgets sliders for Da and R, and a py3Dmol 3D view coloured by RDC sign and magnitude.
Virtual NMR Spectrometer — Shift Predictor Comparison (cells 15–16): Side-by-side HSQC scatter plots (empirical vs SHIFTX2), per-residue Δδ(¹H) bar chart, and a summary statistics table with literature RMSD benchmarks. Graceful fallback when SHIFTX2 is not installed.

Fixed

synth_pdb/physics.py — EnergyMinimizer: Eliminated a spurious WARNING: Forcefield does not support implicitSolvent log message that fired on every run. Root cause: the OBC2 implicit-solvent XML was correctly loaded at construction time, but _create_system_robust also passed implicitSolvent=app.OBC2 as a createSystem() kwarg — which modern OpenMM rejects as unused. Fix: clear self.implicit_solvent_enum after the XML is appended so the kwarg path is never exercised.
synth_pdb/relaxation.py (via synth-nmr>=0.7.2): Heteronuclear NOE values were identical for every residue (a flat horizontal line) because S² cancelled exactly in the ratio cross-relaxation/R₁ when tau_f=0. Fix in synth-nmr 0.7.2: a per-residue fast internal motion timescale tau_f = (1−S²)×500 ps + 50 ps now breaks the cancellation. Flexible termini correctly give low/negative HetNOE; rigid helices give HetNOE ≈ 0.5–0.8. Ref: Lipari & Szabo (1982) J Am Chem Soc 104:4546.
virtual_nmr_spectrometer.ipynb Colab setup: Added explicit pip install synth-nmr>=0.7.2 to the setup cell (was silently skipped because synth-pdb was installed with --no-deps), fixing a ModuleNotFoundError: No module named 'synth_nmr' crash on every fresh Colab runtime.
virtual_nmr_spectrometer.ipynb Neural Shift cell: Added a torch_geometric availability check with a clear install hint (pip install synth-nmr[ml]). Previously the cell crashed with ImportError: torch_geometric is required when the ML extras were absent (the default in Colab).

Changed

Dependency: Tightened synth-nmr lower bound from >=0.6.1 to >=0.7.2 to ensure the HetNOE bug fix and all NMR accuracy improvements are always present.

[1.20.0] - 2026-02-21

Changed

Numpy Compatibility: Relaxed numpy dependency pin to <3.0.0 to resolve binary incompatibility errors (numpy.dtype size changed) in Google Colab and other environments using numpy 2.x.
Dependency Update: Bumped synth-nmr dependency to >=0.6.1 to incorporate upstream numpy compatibility fixes.

[1.19.1] - 2026-02-19

Fixed

PLM Tutorial Bug: Fixed a TypeError in examples/ml_integration/plm_embeddings.ipynb where an obsolete ss_type argument was used instead of conformation for generate_pdb_content().

Changed

Educational Enhancements: Significantly expanded the PLM tutorial notebook (plm_embeddings.ipynb) with plain-language explanations of Protein Language Models, embeddings, similarity metrics, and UMAP clustering for chemists and biologists without machine learning backgrounds.

[1.19.0] - 2026-02-19

Added

PLM Embeddings: Integrated ESM-2 protein language model support via synth_pdb.quality.plm. Generates per-residue and pooled embeddings from generated structures, enabling zero-shot quality scoring and downstream ML tasks.
PLM Tutorial: Added examples/ml_integration/plm_embeddings.ipynb Colab-compatible notebook demonstrating ESM-2 embedding extraction and visualization.
New optional dependency group [plm] (torch>=2.0.0, transformers>=4.30.0).

[1.18.0] - 2026-02-19

Added

GNN Quality Scorer: New synth_pdb.quality.gnn module with a Graph Neural Network model for protein structure quality assessment. Nodes represent residues; edges encode sequence proximity and spatial contacts.
GNN Training Script: scripts/train_gnn_quality.py for training the GNN on labelled structure datasets.
Random Forest Baseline: Included alongside GNN as an interpretable quality-filter baseline (synth_pdb.quality.rf_model).
New optional dependency group [gnn] (torch>=2.0.0, torch_geometric>=2.4.0, scikit-learn, joblib).

Changed

[ai] optional-dependency group now covers the Random Forest model; [gnn] covers the full GNN stack.

[1.17.0] - 2026-02-11

Changed

NMR Package Integration: NMR functionality now provided by the synth-nmr package
Maintained 100% backward compatibility via compatibility shims
All existing code continues to work without changes

Added

Dependency on synth-nmr>=0.1.0

Removed

~1,200 lines of duplicate NMR code (now imported from synth-nmr)

[1.15.0] - 2026-02-02

Added

ML Handover Notebooks: Added zero-copy handover examples for JAX, MLX, and PyTorch in examples/ml_loading/.
Vectorized Batch Generation: Exposed BatchedGenerator and BatchedPeptide via synth_pdb.generator for high-performance AI training pipelines.
Salt Bridge Consolidation: Unified salt bridge force parameters to prevent global parameter conflicts in complex structures.

Fixed

Cyclic Peptide Physics: Refined covalent ring closure using a surgical linear-to-cyclic conversion strategy, bypassing OpenMM template matching limitations.
Physics Preprocessing: Resolved an UnboundLocalError in the simulation engine that caused crashes in specific edge-case topologies.
Notebook Robustness: Added graceful dependency checks and precision-safe assertions (assert_allclose) to ML handover notebooks.
Test Stability: Suppressed verbose Numba debug logging and fixed mock assertion failures in the physics test suite.

[1.14.0] - 2026-01-31

Added

D-Amino Acid Support: Support for generating and validating peptides with D-amino acids using the D- prefix in sequences.
PDB Compatibility: Automatic conversion of D-amino acids to standard 3-letter codes (e.g., DAL, DPH).
Educational Enhancements: Detailed comments explaining chiral mirroring and stereochemistry.
New Tests: Comprehensive TDD suite for D-amino acid generation and validation.

[1.13.1] - 2026-01-30

Added

EGF Generation Example: Added a new example script examples/generate_egf.py demonstrating the generation of a complex 53-residue protein with disarmament minimization and synthetic NMR data.

Fixed

Validator Stability: Fixed a critical TypeError in validator.py where terminal caps or incomplete backbone atoms could cause a crash during bond angle validation.
Regression Testing: Added automated regression tests for the validator crash to prevent future regressions.

[1.13.0] - 2026-01-30

Added

Cyclic Peptide Support: Implemented head-to-tail macrocyclization with automated terminal atom removal (OXT/H1-3) and physics-based bond closure.
Numba JIT Acceleration: Integrated @njit compilation for NeRF geometry engines, Lipari-Szabo spectral density, and Ring Current calculations, achieving 50-100x speedups.
Visual Connectivity: Automated CONECT record generation for cyclic bonds and disulfide bridges to ensure seamless representation in the 3D viewer.
Educational References: Added seminal scientific citations for macrocyclization (Horton, Craik) and deep-dive biophysical commentary to the codebase and README.

Fixed

Proline Minimization: Resolved a bug where Proline residues in cyclic peptides caused OpenMM template errors by stripping illegal amide hydrogens.
Metadata Persistence: Fixed an issue where PTM residue names (SEP, TPO, PTR) were lost during the minimization-to-assembly pipeline.

[1.12.0] - 2026-01-29

Added

Beta-Turn Geometries: Implemented physics-based construction for Type I, II, I', II', and VIII beta-turns. Added --structure CLI argument (e.g., '3-6:typeII') for precise loop modeling.
J-Coupling Prediction: Added generation of \(^3J_{H_NH_\alpha}\) scalar couplings using the Karplus equation (\(A \cos^2\phi + B \cos\phi + C\)). Output available via main.py (CSV export).
Cis-Proline Isomerization: Added --cis-proline-frequency to simulate biologically realistic non-canonical conformations (~5% frequency).
Post-Translational Modifications (PTMs): Added --phosphorylation-rate to simulate Ser/Thr/Tyr phosphorylation, converting residues to SEP/TPO/PTR for downstream MD/NMR analysis.
Performance: Vectorized geometry kernels and improved OpenMM platform selection (CUDA/Metal preference with CPU fallback).

Fixed

CLI Regressions: Fixed AttributeError caused by missing CLI arguments for new biophysics features.
Variable Scoping: Resolved NameError in generator.py related to rotamer selection aliases.

[1.11.0] - 2026-01-29

Added

Pre-Proline Backbone Realism: Implemented specific conformational sampling for residues preceding Proline (favoring Extended/Beta, restricting Alpha). This significantly reduces steric clashes.
Biophysical Efficiency: Validated that improving backbone realism reduces energy minimization time by >60% (2.42s -> 0.91s) by providing physically sound starting structures.
Advanced Chemical Shifts: Added Ring Current Effects (Haigh-Mallion point-dipole model) to chemical shift prediction. Protons above aromatic rings are now correctly shielded, and in-plane protons deshielded.
SASA-Modulated Relaxation: Implemented Solvent Accessible Surface Area (SASA) calculation to modulate Order Parameters (\(S^2\)). Buried residues are now modeled as more rigid than exposed ones.
SSBOND Robustness: Enhanced disulfide bond detection with strict 1-to-1 pairing logic and a defined capture radius (8.0 Å) to prevent multi-bond artifacts in dense structures.

Fixed

SSBOND Regression: Fixed an issue where single Cysteines could form multiple disulfide bonds.
SASA Calculations: Added robust handling for NaN values in SASA calculation for small/mock structures.

[1.10.0] - 2026-01-28

Added

Full Rotamer Library: Expanded backbone-dependent rotamer library to support All 20 Standard Amino Acids (previously limited). Includes charged (ARG, LYS, GLU, ASP) and aromatic residues with biophysically accurate probabilities.
Side-Chain Validation: Implemented validate_side_chain_rotamers() in PDBValidator. It now checks if generated Chi1/Chi2 angles conform to the library distributions (with configurable tolerance).
Chirality Validation: Added validate_chirality() to ensure L-amino acid stereochemistry (checking improper dihedrals).
Validation Integration: Updated CLI (main.py) to run the full suite of validation checks (including rotamers and chirality) whenever --validate, --best-of-N, or --guarantee-valid is used.
Educational Notes: Added extensive comments explaining Rotamer libraries, Staggered conformations, and Validation logic.

Changed

CLI Robustness: Refactored main.py validation calls to use validator.validate_all(), ensuring no checks are silently skipped in the future.
Tests: Replaced incomplete mocks with robust TDD cases for rotamer violations.
Project Config: Updated pyproject.toml to fix setuptools deprecation warnings (retaining backward compatibility).

Fixed

Missing Validation: Fixed an issue where main.py was selectively running only some validation checks, ignoring newly added ones.

[1.9.0] - 2026-01-27

Added

Feature: Metal Ion Coordination (Zinc detection and injection).
Feature: Disulfide Bond detection (SSBOND records).
Feature: Salt Bridge stabilization in Energy Minimization.

[1.8.0] - 2026-01-20

Added

Feature: NEF (NMR Exchange Format) IO support.
Feature: Chemical Shift Prediction (SPARTA+ style logic).