Analyzing Peptide Torsional Dynamics: An Angular-Displacement PCA Pipeline for Short-Horizon Prediction from...

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Biophysics

Background:

• Analyzing short peptide conformational dynamics using molecular dynamics (MD) simulations is complex due to high-dimensional torsional space and periodic dihedral angles.
• Existing methods struggle with statistical analysis and dimensionality reduction of these complex dynamics.
• Characterizing rapid torsional reorganization events requires specialized analytical approaches.

Purpose of the Study:

• To develop an integrated computational workflow for characterizing torsional reorganization patterns in short peptides.
• To introduce a novel angular-displacement representation (χ) to address the challenges of periodic dihedral angles in MD simulations.
• To quantitatively compare different coordinate representations for their ability to preserve dynamical information.

Main Methods:

• All-atom MD simulations combined with a multistage analytical framework.
• Development and application of an angular-displacement representation (χ) for torsional variables.
• Spatiotemporal principal component analysis (PCA) applied to transformed coordinates.
• Quantitative comparison of dihedral angles, sine-cosine embedding, and χ using the VAMP score.

Main Results:

• The angular-displacement representation (χ) acts as a high-pass filter, effectively highlighting rapid torsional reorganizations.
• Quantitative comparison using VAMP score shows χ complements sine-cosine coordinates in capturing different aspects of peptide dynamics.
• PCA analysis of χ reveals stable, reduced representations of collective torsional patterns.
• Application to DENV-2 peptide identified hierarchical flexibility patterns and enabled short-term structural prediction with low error.

Conclusions:

• The proposed workflow offers a computationally efficient method for analyzing torsional reorganization dynamics in peptide simulations.
• The angular-displacement representation (χ) is a valuable tool for dissecting rapid conformational changes in peptides.
• This approach enhances the understanding of peptide flexibility and short-term structural evolution from MD data.