HelixSide: A Comprehensive Method for Local and Global Orientational Analysis of Proteins

Area of Science:

• Structural Biology
• Biophysics
• Computational Biology

Background:

• Protein secondary structure orientation is key to understanding protein structure, function, and interactions.
• Existing methods for quantifying helical geometry lack comprehensive analysis of relative orientations.

Purpose of the Study:

• To introduce HelixSide, a novel computational method for systematically quantifying geometrical metrics of helical secondary structures.
• To develop and validate a new metric, the "side angle," for characterizing secondary structure orientation.
• To demonstrate the utility of HelixSide in analyzing protein tertiary structures and conformational states.

Main Methods:

• HelixSide systematically quantifies geometrical metrics of helical secondary structures, including tilt and kink angles.
• Introduces the "side angle" to characterize the orientation of secondary structure motifs relative to each other or the helical axis.
• Computes metrics at single-residue and whole-protein levels for local and global conformational analysis.

Main Results:

• HelixSide successfully quantifies various geometrical metrics of helical secondary structures.
• The "side angle" provides new insights into the relative orientation of secondary structure elements.
• Case studies on insulin receptor and glycophorin A demonstrate HelixSide's ability to capture tertiary structural characteristics and compare conformational states.

Conclusions:

• HelixSide offers a comprehensive approach to quantifying helical secondary structure geometry.
• The "side angle" is a valuable new metric for structural analysis.
• HelixSide is a versatile, open-source tool applicable to diverse protein types and data sources, including machine learning applications.