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[F.sub.1][F.sub.o]-ATP synthase is the enzyme responsible for most of the ATP synthesis in living systems. The catalytic domain [F.sub.1] of the [F.sub.1][F.sub.o] complex, [F.sub.1]-ATPase, has the ability to hydrolyze ATP. A fundamental problem in the development of a detailed mechanism for this enzyme is that it has not been possible to determine experimentally the relation between the ligand binding affinities measured in solution and the different conformations of the catalytic [beta] subunits ([[beta].sub.TP], [[beta].sub.DP],[[beta].sub.E]) observed in the crystal structures of the mitochondrial enzyme, M[F.sub.1]. Using free energy difference simulations for the hydrolysis reaction ATP+[H.sub.2]O [right arrow] ADP+[P.sub.i] in the [[beta].sub.TP] and [[beta].sub.DP] sites and unisite hydrolysis data, we are able to identify [[beta].sub.TP] as the 'tight' ([K.sub.D] = [10.sup.-12] M, M[F.sub.1]) binding site for ATP and [[beta].sub.DP] as the 'loose' site. An energy decomposition analysis demonstrates how certain residues, some of which have been shown to be important in catalysis, modulate the free energy of the hydrolysis reaction in the [[beta].sub.TP] and [[beta].sub.DP] sites, even though their structures are very similar. Combined with the recently published simulations of the rotation cycle of [F.sub.1]-ATPase, the present results make possible a consistent description of the binding change mechanism of [F.sub.1]-ATPase at an atomic level of detail.

The anomeric ratio for D-xylose in aqueous solution was investigated by applying standard molecular dynamics (MD) and free energy simulations for the two anomers of D-xylopyranose in aqueous solution. All simulations employed the CHARMM molecular mechanics program. The simulations predicted a small free energy difference between the anomers, which results from the cancellation of an intramolecular term that favors the alpha anomer, indicating that the experimental value favors the beta form. The validity of the results were evaluated by performing a direct evaluation of the energy difference and its components from standard MD simulations of each anomer.

The effects of subnanosecond internal motions on proton-proton cross relaxation are investigated using the cyclic decapeptide antamanide (-Val1-Pro2-Pro3-Ala4-Phe5-Phe6-Pro7-Pro8-Phe9-Phe10-) in chloroform. An 800-ps molecular dynamics simulation of the antamanide shows that most of these effects may be illustrated by using a product approximation which distinguishes between radial and angular order parameters and an internal correlation time.

A study was conducted to develop novel protein parameters for the all-atom empirical energy function in the CHARMM program. The parameter evaluation focused on a self-consistent approach designed to realize a balance between the internal and interaction terms of the force field and interactions associated with solvents and solutes. The parameters were then obtained by fitting an extended set of experimental and ab initio results. In addition, internal parametrizations were selected to duplicate geometries from crystal structures, Raman spectroscopic data and ab initio computations.

The SPASIBA force field is parametrized for a large variety of chemical groups. It is shown that the refinement of the force field parameters using the spectroscopic data leads to a better prediction of various physical properties leading particularly to confidence when used in molecular dynamics simulations of molecules with biological interest including various chemical groups such as peptido-glycans or phospholipids.

The free-energy change in a system represented by an empirical energy function, when calculated by thermodynamic integration from the initial to the final state, can be expressed as a sum of "free-energy components," that correspond to contributions from different energy terms or different parts of the system. Although the overall free energy is path independent, the values of the components depend on the integration path, which determines the physical processes involved in the change. A cumulant expansion is used to express the total free-energy change as a sum of terms that contain the cumulants of a single energy term plus a coupling term involving cumulants of more than one energy term. The dependence of the free-energy components on the thermodynamic integration path is shown to arise from the different partitionings of the latter term. A concerted linear integration path, along which the total energy function changes from the initial to the final state as a linear function of an external parameter λ, as well as piecewise-linear paths, along which individual energy terms are changed linearly, are examined. Along the concerted linear path the partitioning of the coupling term preserves permutation symmetry with respect to energy components to all orders. This contrasts to piecewise-linear paths, where the total coupling is projected onto one component. To illustrate the analysis, calculations are made for the transformation. Cl[SUP(0) → Br[SUP(-)] (a neutral particle with the van der Waals parameters of Cl[SUP(-)] to a charged particle with the van der Waals parameters of Br[SUP(-)]) in aqueous solution along various paths. Terms through third order in the cumulant expansion for the change in the solvation free energy are evaluated by use of the reference interaction site model with the hypernetted chain closure, and the values obtained along the linear and piecewise-linear paths are compared and analyzed. The utility of cumulants for the... [ABSTRACT FROM AUTHOR]

Vibrational force fields for the ground states of 1,3-butadiene, 1,3,5-hexatriene, and 1,3,5,7-octatetraene are calculated from extended Pariser–Parr–Pople CI theory. For the ground state of butadiene, the principal π-system force constants are compared to those determined by empirical, other semiempirical, and ab initio methods. The calculated vibrational frequency shifts for a series of deuterium substituted butadienes are found to be in good agreement with experiment. Trends in the principal π-system force constants of the polyenes for the ground states of ethylene through octatetraene are described, including the effects of introducing cis linkages in the polyene chain and of using single- vs single-plus-double-excitation CI. Correlations between the force constants and the calculated vibrational frequencies are discussed, and current assignments of the vibrational spectra of the polyenes are examined in view of the theoretical results. [ABSTRACT FROM AUTHOR]

Vibrational analyses of the ground and lowest excited singlet states of styrene are performed using an extended PPP-CI model. Franck–Condon factors calculated from the model are used to analyze the intensity distribution of the ultraviolet absorption bands of the jet-cooled molecule from 34 000–46 000 cm-1. For the weak first absorption system (S1←S0) the small amount of vibrational excitation found experimentally is well described by the theoretical model. The relatively intense second absorption band shows more extended vibrational development. The model predicts that two electronic transitions S2←S0 and S3←S0 contribute to the absorption spectrum in this region and that a large number of vibrational excitations involving carbon–carbon stretching motions are active. For the S1←S0 and S2←S0 transitions a refinement of the theoretical model is performed to calculate the excited state equilibrium geometries from the measured spectra. Because of the large number of vibrations and the evidence for mixing among them in the excited states (Duschinsky effect), the full multimode treatment of the ground and excited state dynamics is required for an analysis of the spectrum. [ABSTRACT FROM AUTHOR]