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Exploring SARS-CoV-2 spike protein mutations through genetic algorithm-driven structural modeling.

Valentina Di Salvatore1, Avisa Maleki1, Babak Mohajer2

  • 1Department of Drug and Health Sciences, University of Catania, Catania, 95125, Italy.

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|November 21, 2025
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Summary
This summary is machine-generated.

This study introduces a genetic algorithm (GA) for optimizing SARS-CoV-2 spike protein structures, focusing on stability and binding properties. The computational method refines protein models in silico to aid future variant monitoring and vaccine development.

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Area of Science:

  • Computational biology
  • Structural biology
  • Virology

Background:

  • The rapid evolution of SARS-CoV-2 necessitates advanced computational methods to understand mutations in the spike protein.
  • Assessing the impact of mutations on viral stability and receptor binding is crucial for predicting viral behavior and developing countermeasures.

Purpose of the Study:

  • To present a genetic algorithm (GA) framework for the structural optimization of SARS-CoV-2 spike protein variants.
  • To focus on energetic and binding properties of spike protein variants, rather than direct evolutionary prediction.
  • To demonstrate a computational approach for refining protein models and exploring mutation effects in silico.

Main Methods:

  • Application of a genetic algorithm (GA) pipeline for structural optimization of spike protein variants.
  • Evaluation of discrete optimized protein energy (DOPE) scores to assess structural stability across generations.
  • Calculation of Gibbs free energy and binding affinity for spike protein-Angiotensin-converting enzyme 2 (ACE2) receptor interactions.

Main Results:

  • The GA pipeline successfully generated spike variants with improved structural stability, indicated by decreasing DOPE scores.
  • Candidate conformations with favorable thermodynamic properties were identified through analysis of Gibbs free energy and binding affinity.
  • The study demonstrated the algorithm's capability to refine protein models and explore potential mutation effects computationally.

Conclusions:

  • The developed GA framework provides a methodological approach for in silico structural modeling of SARS-CoV-2 spike mutations.
  • This computational strategy can be integrated with evolutionary and experimental data to enhance variant monitoring and vaccine development efforts.
  • While not validating against naturally emerging variants, the study confirms the feasibility of using GA for exploring viral protein mutation landscapes.