Abstract
Protein solubility and conformational stability are a result of a balance of interactions both within a protein and between protein and solvent. The electrostatic solvation free energy of oligoglycines, models for the peptide backbone, becomes more favorable with an increasing length, yet longer peptides collapse due to the formation of favorable intrapeptide interactions between CO dipoles, in some cases without hydrogen bonds. The strongly repulsive solvent cavity formation is balanced by van der Waals attractions and electrostatic contributions. In order to investigate the competition between solvent exclusion and charge interactions we simulate the collapse of a long oligoglycine comprised of 15 residues while scaling the charges on the peptide from zero to fully charged. We examine the effect this has on the conformational properties of the peptide. We also describe the approximate thermodynamic changes that occur during the scaling both in terms of intrapeptide potentials and peptide-water potentials, and estimate the electrostatic solvation free energy of the system.
Highlights
The polypeptide chain of proteins collapse in aqueous solvent due to a complex interplay of correlations or effective interactions within the protein, and between the protein and solvent
There remain issues which make a precise quantitative argument for the contribution of the backbone versus side chains based on the transfer model difficult [10,11,12,13]
We describe the results in terms of the effects that the variations in potential have on the structure followed by a detailed examination of the accompanying thermodynamic changes, and end with our conclusions
Summary
The polypeptide chain of proteins collapse in aqueous solvent due to a complex interplay of correlations or effective interactions within the protein, and between the protein and solvent. Salt effects can stabilize the fold, or destabilize it, based on the overall electrostatics and the interplay with solvent forces [1]. Similar mechanisms have been observed to cause changes in peptide and protein solubility as well [2,3,4]. The transfer model can be used to qualitatively describe the changes in free energy when the solubility or structure of a protein changes with respect to a solvent [8]. Bolen and co-workers used a variant of the transfer model to show that backbone-solvent interactions are a major contributor to the free energy changes during protein folding [9, 10]. There remain issues which make a precise quantitative argument for the contribution of the backbone versus side chains based on the transfer model difficult [10,11,12,13]
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