Rigid-body oscillations of α-helices: implications for protein thermal stability

Abstract

A quasi-continuity model protein consisting of two α-helices undergoing rigid-body torsional oscillations demonstrates that factors stabilizing the model protein, such as increased helix rigidity and hydrophobicity, are the same factors that stabilize thermophilic proteins relative to their mesophilic analogs. The model predicts oscillatory motions with frequencies in the microwave (10 10 Hz) range. These oscillations decrease in frequency with increasing helix rigidity because of compensating increases in the force constant and moment of inertia, thus explaining the retention of activity in the more rigid thermophilic enzymes. Implications for protein design, based on the predictions of the model, are discussed.