Enthalpy of helix-coil transition: missing link in rationalizing the thermodynamics of helix-forming propensities of the amino acid residues.
It is known that different amino acid residues have effects on the thermodynamic stability of an alpha-helix. The underlying mechanism for the thermodynamic helical propensity is not well understood. The major accepted hypothesis is the difference in the side-chain configurational entropy loss upon helix formation. However, the changes in the side-chain configurational entropy explain only part of the thermodynamic helical propensity, thus implying that there must be a difference in the enthalpy of helix-coil transition for different residues. This work provides an experimental test to this hypothesis. Direct calorimetric measurements of folding of a model host peptide in which the helix formation is induced by metal binding is applied to a wide range of residue types, both naturally occurring and nonnatural, at the guest site. Based on the calorimetric results for 12 peptides, it was found that indeed there is a difference in the enthalpy of helix-coil transition for different amino acid residues, and simple empirical rules that define these differences are presented. The obtained difference in the enthalpies of helix-coil transition complement the differences in configurational entropies and provide the complete thermodynamic characterization of the helix-forming tendencies.
Richardson
John M
JM
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Lopez
Maria M
MM
Makhatadze
George I
GI
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D004355:Drug Stability; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D000596:Amino Acids; D010455:Peptides