A Comprehensive Study of Factors Affecting the Prediction of the pK a Shift of Asp26 in Thioredoxin Protein

The stable protonation state of ionizable amino acids in a protein can be predicted by computing the pK a shift of that residue within the protein environment. Thermodynamic Integration (TI) is an ideal molecular dynamics-based approach for predicting the pK a shift of ionizable protein residues. He...

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Veröffentlicht in:The journal of physical chemistry. B 2024-08, Vol.128 (30), p.7304-7312
Hauptverfasser: Verma, Shivani, Nair, Nisanth N.
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Nair, Nisanth N.
description The stable protonation state of ionizable amino acids in a protein can be predicted by computing the pK a shift of that residue within the protein environment. Thermodynamic Integration (TI) is an ideal molecular dynamics-based approach for predicting the pK a shift of ionizable protein residues. Here, we probe TI-based simulation protocols for their ability to accurately predict the pK a shift of Asp26 in thioredoxin. While implicit solvent models can predict the pK a shift accurately, explicit solvent models result in substantial errors. To understand the underlying reason for this surprising discrepancy, we investigate the role of various factors such as solvent models, conformational sampling, background charges, and polarization.
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title A Comprehensive Study of Factors Affecting the Prediction of the pK a Shift of Asp26 in Thioredoxin Protein
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