Exploring complexity of class-A Beta-lactamase family using physiochemical-based multiplex networks

Area of Science:

• Biochemistry
• Computational Biology
• Protein Science

Background:

• Beta-lactamase enzymes are crucial in antibiotic resistance, conferring protection against beta-lactam antibiotics.
• Understanding the evolutionary and functional constraints of the Beta-lactamase protein family is essential for developing new antimicrobial strategies.

Purpose of the Study:

• To explore the Beta-lactamase protein family using a novel multiplex network approach based on amino acid physiochemical properties.
• To identify key motifs, evolutionary links, and hierarchical property influences within the Beta-lactamase family.

Main Methods:

• A multiplex network representation of Beta-lactamase multiple sequence alignment was employed.
• Network layers were derived from physiochemical properties (polarity, hydrophobicity, polarizability, volume) of amino acids.
• Node multi-degree analysis was used to assess hierarchical property influence.

Main Results:

• Identified aggregation of nodes with similar property signs, indicating functional and evolutionary constraints.
• Observed distinct distributions of evolutionary links across layers, with polarity dominant at low thresholds and hydrophobicity at high thresholds.
• Discovered simultaneous connections for polarizability-volume combinations and exclusive shared links for hydrophobicity-polarizability-volume, suggesting significant evolutionary impacts.

Conclusions:

• The multiplex network approach effectively reveals intricate interactions and constraints within the Beta-lactamase family.
• Key properties influencing Beta-lactamase functionality were identified, offering insights for potential drug target development.
• This study provides a foundation for understanding protein evolution and designing novel enzyme modulators.