NATIVE PROTEIN FLUCTUATIONS - THE CONFORMATIONAL-MOTION TEMPERATURE AND THE INVERSE CORRELATION OF PROTEIN FLEXIBILITY WITH PROTEIN STABILITY

We study the fluctuations of native proteins by exact enumeration usin g the HP lattice model. The model fluctuations increase with temperatu re. We observe a low-temperature point, below which large fluctuations are frozen out. This prediction is consistent with the observation by Tilton et al. [R. F. Tilton, Jr., J. C. Dewan, and G. A. Petsko, Bioc hemistry 31, 2469 (1992)], that the thermal motions of ribonuclease A increase sharply above about 200K. We also explore protein ''flexibili ty'' as defined by Debye-Waller-like factors and solvent accessibiliti es of core residues to hydrogen exchange. We find that proteins having greater stability tend to have fewer large fluctuations, and hence lo wer flexibilities. If flexibility is necessary for enzyme catalysis, t his could explain why proteins from thermophilic organisms, which are exceptionally stable, may be catalytically inactive at normal temperat ures.