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Coupling between conformation and proton binding in proteins.

Jorge A Vila¹, Daniel R Ripoll, Yelena A Arnautova

¹Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.

|August 5, 2005

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Accurately predicting protein folding requires careful consideration of charge distribution. For most proteins, a fixed charge model suffices, but some necessitate analyzing all ionization states for accurate native state discrimination.

Area of Science:

Computational Biology
Biophysics
Protein Folding

Background:

Determining native protein conformations is crucial for understanding biological function.
Accurate modeling of electrostatic interactions and solvation free energy is key to predicting protein folding.
The choice of charge distribution model impacts the accuracy of protein folding predictions.

Purpose of the Study:

To compare fixed charge distribution versus proton-binding equilibria models for discriminating native from non-native protein conformations.
To evaluate the role of electrostatic interactions in determining the charge distribution of native protein folds.
To assess the influence of different charge assignment models on protein stability.

Main Methods:

Analyzing the charge distribution of 7 proteins across their conformational ensembles.

Related Experiment Videos

Estimating solvation free energy by exploring all possible ionization states (2^zeta).

Comparing fixed charge distribution models (Generalized Born, Accessible Surface Area) with Poisson equation solutions.

Examining alternative charge assignment models for ionizable residues in 21 native-like proteins.

Main Results:

For 6 out of 7 proteins, the Generalized Born model with fixed charges offered the best accuracy-speed trade-off compared to the Accessible Surface Area model.
For one protein, considering all ionization states was essential for distinguishing native from non-native conformations.
Different charge models yielded significant variations in ionization degree and charge distribution for native folds.
Native state stability depends on a balance of all energy components.

Conclusions:

The choice of charge modeling approach is critical and protein-dependent for accurate folding prediction.
Electrostatic interactions and ionization states significantly influence protein charge distribution and stability.
Conformational entropy and protein dynamics are vital for successful *ab initio* protein folding prediction.