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Abstract
Protein folding evolves by exploring the conformational space with a subtle balance between enthalpy and entropy changes which eventually leads to a decrease of the free energy upon reaching the folded structure.
A complete understanding of this process requires, therefore, a deep insight into both contributions to the free energy.
In this work, we clarify the role of entropy in favoring the stabilization of folded structures in polyalanine peptides with up to 12 residues . We use a novel method referred to as K2V that allows us to obtain the potential energy landscapes in terms of residue conformations extracted from molecular dynamics simulations at conformational equilibrium, and yields folding thermodynamic magnitudes in agreement with the experimental data available.
Our results demonstrate that the folded structures of the larger polyalanine chains are stabilized with respect to the folded structures of the shorter chains mostly by an increase of the entropic contribution of the solvent, which compensates the decrease of conformational entropy of the polypeptide, thus unveiling a key piece in the puzzle of protein folding.
In addition, the ability of the K2V method to provide the enthalpic and entropic contributions for individual residues along the peptide chain makes it clear that the entropic stabilization is basically governed by the nearest neighbor residues conformations, with the folding propensity being rationalized in terms of triads of residues.
A complete understanding of this process requires, therefore, a deep insight into both contributions to the free energy.
In this work, we clarify the role of entropy in favoring the stabilization of folded structures in polyalanine peptides with up to 12 residues . We use a novel method referred to as K2V that allows us to obtain the potential energy landscapes in terms of residue conformations extracted from molecular dynamics simulations at conformational equilibrium, and yields folding thermodynamic magnitudes in agreement with the experimental data available.
Our results demonstrate that the folded structures of the larger polyalanine chains are stabilized with respect to the folded structures of the shorter chains mostly by an increase of the entropic contribution of the solvent, which compensates the decrease of conformational entropy of the polypeptide, thus unveiling a key piece in the puzzle of protein folding.
In addition, the ability of the K2V method to provide the enthalpic and entropic contributions for individual residues along the peptide chain makes it clear that the entropic stabilization is basically governed by the nearest neighbor residues conformations, with the folding propensity being rationalized in terms of triads of residues.
