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A Genetic Programming Approach to Engineering MRI Reporter Genes.

Alexander R Bricco1, Iliya Miralavy2, Shaowei Bo3

  • 1Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan 48823, United States.

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|March 22, 2023
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Summary
This summary is machine-generated.

We developed a novel computational tool, the Protein Optimization Engineering Tool (POET), for protein optimization. POET utilizes convergent evolution to create highly efficient MRI contrast agents and offers broad applications in protein engineering.

Keywords:
CEST MRIgenetic programmingprotein engineering

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Area of Science:

  • Biotechnology
  • Computational Biology
  • Biochemistry

Background:

  • Existing protein engineering methods often rely on divergent evolution.
  • Current methods for developing contrast agents for Magnetic Resonance Imaging (MRI) have limitations in efficiency and sequence diversity.

Purpose of the Study:

  • To develop a novel computational approach for protein optimization.
  • To engineer proteins with enhanced MRI contrast capabilities.
  • To explore new mechanisms of protein function through computational design.

Main Methods:

  • Development of the Protein Optimization Engineering Tool (POET), a genetic programming algorithm.
  • Utilizing a small library of literature values as starting points for optimization.
  • Employing convergent evolution principles within the genetic programming framework.

Main Results:

  • Engineered proteins demonstrated a four-fold increase in MRI contrast compared to state-of-the-art.
  • POET generated peptides with significantly different sequences and chemical environments than existing agents.
  • The novel peptides challenge existing models of contrast-producing peptide function.

Conclusions:

  • POET enables the discovery of highly efficient protein-based imaging agents.
  • The convergent evolution approach expands the possibilities for protein sequence and function discovery.
  • This computational method has wide-ranging applicability in protein engineering beyond imaging agents.