A Protein Co-Conservation Network Model Characterizes Mutation Effects on SARS-CoV-2 Spike Protein

Area of Science:

• Virology
• Computational Biology
• Structural Biology

Background:

• Numerous SARS-CoV-2 variants pose challenges to pandemic control.
• Spike protein mutations are critical for viral attachment and antibody targeting.

Purpose of the Study:

• To develop a sequence-based model to analyze mutation effects on the SARS-CoV-2 spike protein.
• To investigate how mutations alter viral functions using network topology.

Main Methods:

• Developed a protein co-conservation weighted network (PCCN) model.
• Analyzed topological features of mutation sites within the spike protein network.

Main Results:

• Mutation sites exhibit significantly higher centrality than non-mutation sites.
• Changes in stability and binding free energy correlate with network properties like neighbor degree and shortest path length.

Conclusions:

• The PCCN model offers novel insights into SARS-CoV-2 spike protein mutations.
• Network analysis effectively reflects how mutations affect protein function and viral behavior.