A method is described for identifying collective motions in proteins from molecular dynamics trajectories or normal mode simulations. The method makes use of the covariances of atomic positional fluctuations. It is illustrated by an analysis of the bovine pancreatic trypsin inhibitor. Comparison of the covariance and cross-correlation matrices shows that the relative motions have many similar features in the different simulations. Many regions of the protein, especially regions of secondary structure, move in a correlated manner. Anharmonic effects, which are included in the molecular dynamics simulations but not in the normal analysis, are of some importance in determining the larger scale collective motions, but not the more local fluctuations. Comparisons of molecular dynamics simulations in the present and absence of solvent indicate that the environment is of significance for the long-range motions.

Simulations of the residual configurational entropy of a protein in the native state suggest that it is nearly an order of magnitude larger than the entropy of denaturation. The implications of this result are discussed.

The cubane [4Fe-4S] is the most common multinuclear metal center in nature for electron transfer and storage. Using electrospray, we produced a series of gaseous doubly charged cubane-type complexes, [Fe4S4L4]2- (L = -SC2H5, -SH, -Cl, -Br, -I) and the Se-analogues [Fe4Se4L4]2- (L = -SC2H5, -Cl), and probed their electronic structures with photoelectron spectroscopy and density functional calculations. The photoelectron spectral features are similar among all the seven species investigated, revealing a weak threshold feature due to the minority spins on the Fe centers and confirming the low-spin two-layer model for the [4Fe-4S](2+) core and its "inverted level scheme". The measured adiabatic detachment energies, which are sensitive to the terminal ligand substitution, provide the intrinsic oxidation potentials of the [Fe4S4L4]2- complexes. The calculations revealed a simple correlation between the electron donor property of the terminal thiolate as well as the bridging sulfide with the variation of the intrinsic redox potentials. Our data provide intrinsic electronic structure information of the [4Fe-4S] cluster and the molecular basis for understanding the protein and solvent effects on the redox properties of the [4Fe-4S] active sites.