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A new procedure for the analysis of the structure and molecular dynamics of duplex DNA is introduced, in which comprehensive visualization of results and pattern recognition is greatly facilitated. The method involves determining the values of the conformational and helicoidal parameters for each structure entering the analysis using the method "Curves" developed by Lavery and Sklenar, J. Biomol. Str. Dyn. 6, 63 (1988), followed by a novel computer graphic display of the results. The graphic display is organized systematically using conformation wheels, or "dials", for each IUPAC torsional parameter and "windows" on the range of values assumed by the linear and angular helicoidal parameters, and is presented in a form isomorphous with the structure per se. The complete time evolution of the conformational and helicoidal parameters of a DNA double helix can then be depicted in a set of six composite figures. Dynamical aspects of helix bending are also subsumed in this analysis. The procedure is illustrated with an analysis of the structures of canonical A and B forms of DNA and the 300 degrees K native dodecamer duplex d(CGCGAATTCGCG). The "dials and windows" are then used for a comprehensive analysis of 30 psec of molecular dynamics on the dodecamer in the vicinity of a canonical B-DNA energy minimum. This involves presentation of the time evolution of 206 conformational and 230 helicoidal parameters for the dodecamer. A number of interesting structural features can be recognized in the analysis, including crankshaft motions, BI - BII transitions, sugar repuckerings, and a description of spontaneous helix bending at what corresponds to the 1 degrees and 2 degrees "hinge points" indicated in the crystal structure. Our approach is expected to be directly useful for critical analysis of the effects of various assumptions about force field parameters, hydration and electrostatic effects and thus contribute to the development of reliable simulation protocols for nucleic acid systems. Extension of the method to present differential changes in conformational and helicoidal parameters is expected to be valuable for the analysis of structural and molecular dynamics studies of the reorganization and adaptation of DNA on complexation with various drugs and regulatory proteins.

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beta-Lactamase, which catalyzes beta-lactam antibiotics, is prototypical of large alpha/beta proteins with a scaffolding formed by strong noncovalent interactions. Experimentally, the enzyme is well characterized, and intermediates that are slightly less compact and having nearly the same content of secondary structure have been identified in the folding pathway. In the present study, high temperature molecular dynamics simulations have been carried out on the native enzyme in solution. Analysis of these results in terms of root mean square fluctuations in cartesian and [phi, psi] space, backbone dihedral angles and secondary structural hydrogen bonds forms the basis for an investigation of the topology of partially unfolded states of beta-lactamase. A differential stability has been observed for alpha-helices and beta-sheets upon thermal denaturation to putative unfolding intermediates. These observations contribute to an understanding of the folding/unfolding processes of beta-lactamases in particular, and other alpha/beta proteins in general.

Figure 7. Energy requirements for the insertion of formaldehyde into the Co-H bond of ~*-HCO(CO)~-H~CO. All energies are in kJ/mol. The numbers in brackets represent the activation energies for the reaction in the direction of the arrows. The numbers without brackets stand for the energy difference between two isomers, where a positive value indicates that the resulting complex is higher in energy.activation energy of only 55 kJ/mol. As indicated above this route might not produce much methanol, since the migratory shift of the hydroxymethyl group to a carbonyl ligand is, in analogy to the alkyl reaction, a very facile process. VI. Summary and ConclusionsWe have investigated here the geometries of the *-complexes that result from an interaction between formaldehyde and the coordinatively unsaturated cobalt complex HCO(CO)~. Furthermore, the insertion of the coordinated formaldehyde group into the Co-H bond was also studied by determining the geometries of some of the insertion products as well as by evaluating the energy profile of the insertion mechanism by a linear transit procedure.The migratory insertion of formaldehyde into the Co-H bond was shown to produce stable methoxy or hydroxymethyl intermediates. However, the methoxy complexes were 25 to 40 kJ/mol lower in energy. The energy difference was traced to the stronger Co-0 bond of the methoxy ligand. Both types of compounds were stabilized by the formation of an agostic interaction between the shifted hydride and the cobalt center. The migration of the hydride ligand to the carbon atom of the complexes aldehyde molecule was found to have a reaction enthalpy, AE, of 6 kJ/mol and an activation barrier, AE', of less than 5 kJ/mol. These values parallel the results of the ethylene insertion and underline the similarity of the two molecular systems. The alternative process where the hydride ligand migrates to the oxygen atom of the H2C0 group was somewhat disfavored by an endothermicity of 40 kJ/mol and an activation barrier of 15 kJ/mol. However, the energy requirements of the later process are small enough such that both insertion modes are operative under catalytic conditions where the formation of the methoxy intermediate is favored over the hydroxymethyl analogue. The energetics for the insertion process is summarized in Figure 7. Acknowledgment.Abstract: A molecular dynamics (MD) simulation was performed on the hydrated decapeptide Alalo~C50H20 under periodic boundary conditions. The initial configuration of the peptide was a canonical right-handed a-helix. Over the course of the MD trajectory, the helix is overall intact and dynamically stable, except for one position in which incipient helix destabilization is observed. The helix hydrogen bond at this position was first destabilized transiently for -10 ps. Some 35 ps later, a persistent destabilization occurred. Analysis reveals that the helix destabilizations are both accompanied by water insertion in a manner consistent with that recently proposed by Sundaralingan and Sekharudul based on a survey of ...