A many-body term improves the accuracy of effective potentials based on protein coevolutionary data

Area of Science:

• Computational biology
• Biophysics
• Protein structure prediction

Background:

• Correlated mutations in homologous proteins aid in predicting protein structure and developing effective potentials.
• Existing two-body effective potentials capture pairwise amino acid interactions.

Purpose of the Study:

• To extend the two-body effective potential by incorporating a many-body term.
• To improve the prediction accuracy of mutation effects in proteins.

Main Methods:

• Applied a theoretical framework based on the principle of maximum entropy.
• Developed and tested an extended effective potential including a many-body term.
• Evaluated the potential's performance on 308 mutations across 14 proteins, including membrane proteins.

Main Results:

• The extended many-body potential demonstrated superior performance compared to the two-body potential in predicting mutation energetics.
• The parameters of the many-body term showed a correlation with residue hydrophobicity.
• This correlation suggests the many-body term partially models solvent effects.

Conclusions:

• The inclusion of a many-body term significantly enhances the accuracy of effective potentials for predicting mutation effects.
• The developed potential offers a more refined approach to understanding protein stability and function.
• The findings suggest a link between many-body interactions, hydrophobicity, and solvent effects in protein systems.