Propensities, probabilities, and the Boltzmann hypothesis.
The relative strengths of interactions involving polypeptide chains can be estimated with reasonable accuracy with statistical potentials, free-energy functions derived from the frequency of occurrence of structural arrangements of residues or atoms in collections of protein structures. Recent published work has shown that the energetics of side-chain/backbone interactions can be modeled by the phi/psi propensities of the 20 amino acids. In this report, the more commonly used phi/psi probabilities are demonstrated to fail in evaluating the free energies of protein conformations because of an overriding preference for all helical structures. Comparison of the hypothetical reactions implied by these two different statistics-propensities versus probabilities-leads to the conclusion that the Boltzmann hypothesis may only be applicable for the calculation of statistical potentials after the starting conformation has been specified. This conclusion supports a simple conjecture: The surprising success of the Boltzmann hypothesis in explaining the energetics of protein structures is a direct consequence of a real equilibrium, one extending over evolutionary time that has maintained the stability of each protein within a narrow range of values.
Shortle
David
D
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dshort1@jhmi.edu
D000595:Amino Acid Sequence; D003627:Data Interpretation, Statistical; D006860:Hydrogen Bonding; D010455:Peptides / Q000737:chemistry*; D011336:Probability; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D010455:Peptides; D011506:Proteins