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About the Protein Space Vastness.

Jorge A Vila1

  • 1IMASL-CONICET, Universidad Nacional de San Luis, Ejército de Los Andes 950, 5700, San Luis, Argentina. jorgevila84@gmail.com.

The Protein Journal
|November 1, 2020
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Summary
This summary is machine-generated.

Estimating the vast Protein Space is crucial for understanding protein evolution. This study reduces the theoretical size to 10^9 functional proteins and reveals how marginal stability impacts protein evolvability.

Keywords:
AnfinsenMaynard SmithProtein EvolutionProtein Marginal StabilityProtein Space

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Area of Science:

  • Evolutionary Biology
  • Biophysics
  • Protein Science

Background:

  • The theoretical size of the Protein Space (10^130 sequences for a 100-residue protein) presents a challenge for understanding protein evolution.
  • Protein evolvability, the capacity of proteins to evolve new functions, is directly linked to the size and accessibility of this space.

Purpose of the Study:

  • To provide a more realistic estimation of the functional Protein Space size.
  • To estimate the average mutation rate per amino acid.
  • To investigate the role of protein marginal stability in protein evolvability.

Main Methods:

  • A simplified analysis was employed to estimate the number of functional proteins.
  • The average mutation rate per amino acid (ξ) was calculated.
  • The relationship between marginal stability and the availability of sequences for evolution was inferred.

Main Results:

  • The estimated size of the functional Protein Space was reduced from ~10^130 to ~10^9 sequences.
  • A robust average mutation rate per amino acid (ξ ≈ 1.23) was determined.
  • Protein marginal stability was shown to restrict the fraction of sequences available for functional protein evolution at any given time.

Conclusions:

  • This study reframes the Protein Space vastness problem by providing a rational estimate of functional protein numbers.
  • Marginal protein stability significantly impacts and constrains protein evolvability by limiting the accessible sequence space.
  • Understanding these factors is critical for predicting the evolutionary trajectory of proteins.