ResidueDisorder

ResidueDisorder measures intrinsic disorder in proteins and tracks conformational transitions using structural coordinates and molecular dynamics trajectories within the Rosetta software suite.

Key Features:

• Intrinsic Disorder Measurement from Structure: Measures per-residue intrinsic disorder directly from the atomic coordinates of a single protein conformation.
• Benchmark Accuracy: Demonstrated 69.2% accuracy measuring intrinsic disorder from structural data versus 65.4% for sequence-based predictions in a benchmark of 229 proteins spanning 0–100% disorder.
• Conformational Transition Analysis: Analyzes unfolding and folding trajectories by employing steered MD (SMD), high-temperature MD, and accelerated MD (aMD) and correlates root-mean-square deviation (RMSD) relative to the native structure with the fraction of denatured residues.
• Predictive Capabilities: Predicts folding/unfolding transitions and identifies native-like structures from long-timescale molecular dynamics trajectories when crystallographic data are unavailable.

Scientific Applications:

• IDP/IDR Characterization: Characterization of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) by measuring disorder directly from structural data.
• Protein Dynamics Analysis: Analysis of protein dynamics and conformational changes through correlation of RMSD and denaturation metrics across MD trajectories.
• Folding/Unfolding Pathway Exploration: Exploration of folding and unfolding pathways and transitions using long-timescale molecular dynamics simulations.
• Native-like Structure Identification: Identification of native-like structures from MD-generated ensembles in the absence of experimental crystallographic structures.

Methodology:

Computes per-residue disorder from atomic coordinates of single conformations; analyzes molecular dynamics trajectories generated by steered MD (SMD), high-temperature MD, and accelerated MD (aMD); correlates RMSD to the native structure with the fraction of denatured residues; and benchmarks structural disorder measurements against sequence-based predictions on 229 proteins (69.2% vs 65.4%).