ASC-G4, an algorithm to calculate advanced structural characteristics of G-quadruplexes

Area of Science:

• Structural biology
• Bioinformatics
• Computational chemistry

Background:

• G-quadruplexes (G4) are crucial nucleic acid structures with diverse biological roles.
• Accurate determination of G4 structural characteristics is essential for understanding their function.
• Existing methods for G4 analysis present ambiguities in topology and parameter calculation.

Purpose of the Study:

• To introduce ASC-G4, an algorithm for unambiguous calculation of advanced G4 structural characteristics.
• To resolve ambiguities in G4 topology and guanine glycosidic configuration determination.
• To provide a user-friendly web tool for comprehensive G4 structure analysis.

Main Methods:

• Development of the ASC-G4 algorithm based on oriented strand numbering.
• Application of ASC-G4 to analyze a dataset of 207 G4 structures.
• Creation of a web server (http://tiny.cc/ASC-G4) for automated G4 structure analysis.

Main Results:

• ASC-G4 enables unambiguous determination of intramolecular G4 topology and guanine glycosidic configuration.
• Demonstrated that C3' or C5' atoms are more appropriate than P atoms for groove width calculation.
• Identified minimum groove width as a more accurate measure of available space within G4 grooves.
• Analysis of 207 G4 structures guided algorithm refinement and parameter choices.

Conclusions:

• ASC-G4 provides a robust and comprehensive method for G4 structural analysis.
• The developed web tool facilitates detailed investigation of G4 topology, loops, bulges, and atomic parameters.
• ASC-G4 enhances the evaluation of G4 structure quality through various distance metrics.