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Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
Published on: January 26, 2024
Protein-protein binding is often associated with changes in protonation state.
1Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA.
Proteins
|October 13, 2007
Summary
Protein-protein binding frequently alters amino acid residue protonation states. This change significantly impacts binding energy calculations, especially when considering pH effects.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Protein-protein interactions are crucial for cellular functions.
- Accurate calculation of binding energy requires considering residue protonation states.
- Protonation states are pH-dependent and can change upon complex formation.
Purpose of the Study:
- To calculate pK(a) values for ionizable residues in protein complexes and their free forms.
- To quantify changes in residue and net protonation states upon complex formation.
- To assess the impact of these changes on binding energy calculations.
Main Methods:
- Utilized the PROPKA method to determine pK(a) values.
- Analyzed structures of 75 protein-protein complexes and their unbound counterparts.
- Computed changes in protonation states and pH-dependent binding energy corrections.
Main Results:
- Protein-protein binding induced significant protonation state changes in a substantial portion of cases (up to 77% for individual residues and 61% for net charge).
- Analysis using unbound structures indicated higher incidence of protonation changes compared to bound structures.
- pH-dependent corrections to binding energy were significant, affecting binding constants in up to 45% of cases.
Conclusions:
- Protein-protein binding is frequently associated with alterations in amino acid residue protonation and net protein charge.
- The choice of reference structure (unbound vs. bound) influences the estimation of protonation changes.
- Accounting for pH-dependent protonation changes is essential for accurate binding energy calculations in protein complexes.
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