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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]

Lubricant distribution on test disks for hard drives has been examined with angle-resolved ESCA. The lubricant partitions itself into thin, presumably monolayer, areas and thicker patches largely impenetrable to the substrate photoelectrons. These thicker regions are at least three times as thick as the monolayer and may correspond to the trilayers detected by surface energy and ellipsometric surface diffusion measurements. Detailed examination of layering within the lubricant shows significant perfluoropolyether (Zdol) backbone and a discernible excess of ether oxygen adjacent to the overcoat surface. The latter results indicate that the inverted-U conformation sometimes sketched for bonded lubricants is an exaggeration for the system examined here. The analysis models include a two-tiered overlayer structure (thin and thick) and a two-slab structure for revealing subtle layering within the thin regions. Current office spreadsheets provide adequate visualization and optimization capability for performing these analyses. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Abstract: A semiclassical trajectory approach has been used to study the cis–trans isomerization from the triplet state of butene-2. It is found that use of the full conformational space for the trajectory calculation permits one to demonstrate that a simplified treatment is applicable; namely, once a transition from the triplet to the ground-state singlet has taken place, return to the triplet is prevented by rapid redistribution of the available energy. The method is used to determine the dependence of the isomerization rate on the essential parameters of the system. [Copyright &y& Elsevier]

Analyzes the anomeric equilibrium for d-xylose in aqueous solution using standard molecular dynamics (MD) and free energy simulations. Result of the thermodynamic integration analysis of the components; Confirmation of the validity of the partitioning by direct evaluation of the energy difference and its components from long standard MD simulations of each anomer.

Presents a review of information that focuses on the methodology of molecular dynamics and its applications to biological problems. Definition; Potential energy function; Simulation methods; Experimental verification; Macromolecular motions; Functionally relevant motions; Limitations and prospects. INSET: Myoglobin and haemoglobin; Photosynthetic reaction centre....

An understanding of the various states available to a polypeptide chain is important for a description of the protein folding process. We use a 16-monomer chain on a two-dimensional square lattice to model a protein. This makes it possible to enumerate all self-avoiding conformations from which any equilibrium thermodynamic quantity can be calculated. By varying the external conditions of temperature and average attraction, we construct a phase diagram for the model protein. It is found to have an extended coil state, a homopolymer-like disorganized globule state, and an organized frozen globule state that corresponds to the lowest energy (native) conformation. The exact model results agree well with analytical heteropolymer theory. [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]

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen. [ABSTRACT FROM AUTHOR]

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality Fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen. [ABSTRACT FROM AUTHOR]

SUMMARY From the S-wave data collected along a 270-km-long profile spanning the Kunlun mountains in NE Tibet, 14595 Sg phase arrivals and 21 SmS phase arrivals were utilized to derive a whole-crustal S velocity model and, together with a previously derived P velocity model, a Poisson's ratio (σ) model beneath the profile. The final tomogram for the upper 10-15 km of the crust reveals the lower velocities associated with the predominantly Neogene-Quaternary sediments of the Qaidam basin to the north and the higher velocities associated with the predominantly Palaeozoic and Mesozoic upper crustal sequences of the Songpan-Ganzi terrane and Kunlun mountains to the south. This study finds no evidence that the Kunlun mountains are involved in large-scale northward overriding of the Qaidam basin along a shallow south-dipping thrust. The σ in the upper 10-15 km of the crust are often lower than 0.25, indicating a preponderance of quartz-rich rocks in the upper crust beneath the profile. Below 10-15 km depth, the remainder of the crust down to the Moho has an average σ of 0.24 beneath the Songpan-Ganzi terrane and Kunlun mountains and 0.25 below the Qaidam basin. These low σ are similar to other low σ found along other profiles in the northeastern part of the plateau. Assuming an isotropic situation and no significant variation in σ between 10-15 km depth and the Moho, then the lower crust between 25-30 km depth below sea level and the Moho with P velocities varying from 6.6 km s−1 at the top to around 6.9 km s−1 at the base and σ of 0.24-0.25 should comprise intermediate granulites in the upper part transitioning to granulite facies metapelites in the lower part. As the pre-Cenozoic Qaidam basin crust has probably not lost any of its lower crust during the present Himalayan orogenic cycle in the Cenozoic and only has a σ of 0.245-0.25, then it appears that the pre-Cenozoic Qaidam basin crust involved in the collision is more felsic and thus weaker and more easily deformable than normal continental crust with a global average σ of 0.265-0.27 and the Tarim and Sichuan basin crusts. This situation then probably facilitates the collision and promotes the formation of new high plateau crust at the NE margin of Tibet. South of the Qaidam basin, the crust of the Songpan-Ganzi terrane and Kunlun mountains has an even lower average crustal σ of 0.23-0.24 and is thus presumably even weaker and more easily deformable than the crust beneath the Qaidam basin. This then supports the hypothesis of Karplus et al. that 'the high Tibetan Plateau may be thickening northward into south Qaidam as its weak, thickened lower crust is injected beneath stronger Qaidam crust'. [ABSTRACT FROM AUTHOR]

The rigor to post-rigor transition in myosin, a consequence of ATP binding, plays an essential role in the Lymn-Taylor functional cycle because it results in the dissociation of the actomyosin complex after the powerstroke. On the basis of the X-ray structures of myosin V, we have developed a new normal mode superposition model for the transition path between the two states. Rigid-body motions of the various subdomains and specific residues at the subdomain interfaces are key elements in the transition. The allosteric communication between the nucleotide binding site and the U50/L50 cleft is shown to result from local changes due to ATP binding, which induce large amplitude motions that are encoded in the structure of the protein. The triggering event is the change in the interaction of switch I and the P-loop, which is stabilized by ATP binding. The motion of switch I, which is a relatively rigid element of the U50 subdomain, leads directly to a partial opening of the U50/L50 cleft; the latter is expected to weaken the binding of myosin to actin. The calculated transition path demonstrates the nature of the subdomain coupling and offers an explanation for the mutual exclusion of ATP and actin binding. The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central b-sheet in the rigor to post-rigor transition is described. [ABSTRACT FROM AUTHOR]

A method is proposed for the estimation of absolute binding free energy of interaction between proteins and ligands. Conformational sampling of the protein-ligand complex is performed by molecular dynamics (MD) in vacuo and the solvent effect is calculated a posteriori by solving the Poisson or the Poisson–Boltzmann equation for selected frames of the trajectory. The binding free energy is written as a linear combination of the buried surface upon complexation, SASbur, the electrostatic interaction energy between the ligand and the protein, Eelec, and the difference of the solvation free energies of the complex and the isolated ligand and protein, ΔGsolv. The method uses the buried surface upon complexation to account for the non-polar contribution to the binding free energy because it is less sensitive to the details of the structure than the van der Waals interaction energy. The parameters of the method are developed for a training set of 16 HIV-1 protease-inhibitor complexes of known 3D structure. A correlation coefficient of 0.91 was obtained with an unsigned mean error of 0.8 kcal/mol. When applied to a set of 25 HIV-1 protease-inhibitor complexes of unknown 3D structures, the method provides a satisfactory correlation between the calculated binding free energy and the experimental pIC50 without reparametrization. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Turning of infants during phototherapy for hyperbilirubinemia is practiced in many nurseries. However, there is little research evidence in support of this practice. This study examined the effect of turning on serum total bilirubin concentration and on the duration of phototherapy. STUDY DESIGN: We first conducted a pilot study in term infants requiring phototherapy using transcutaneous bilirubinometry in order to determine the time required to clear the skin of bilirubin. This "blanching time" was found to be approximately 150 minutes. We then conducted a randomized study comparing turning the baby during phototherapy with care in the supine position only. RESULTS: Thirty term infants were enrolled in the study (turned -- 14; supine -- 16). No differences were found between the groups in baseline data, such as birth weight, gestational age, age at start of phototherapy, or type of feeds. Infants in the supine group showed a significantly larger drop in serum total bilirubin concentration and required a shorter duration of phototherapy. CONCLUSION: We conclude that infants should be nursed supine during phototherapy. Based on these results, we propose a modification to the traditional model of bilirubin kinetics during phototherapy. [ABSTRACT FROM AUTHOR]

The flexibility of different regions of HIV-1 protease was examined by using a database consisting of 73 X-ray structures that differ in terms of sequence, ligands or both. The root-mean-square differences of the backbone for the set of structures were shown to have the same variation with residue number as those obtained from molecular dynamics simulations, normal mode analyses and X-ray B-factors. This supports the idea that observed structural changes provide a measure of the inherent flexibility of the protein, although specific interactions between the protease and the ligand play a secondary role. The results suggest that the potential energy surface of the HIV-1 protease is characterized by many local minima with small energetic differences, some of which are sampled by the different X-ray structures of the HIV-1 protease complexes. Interdomain correlated motions were calculated from the structural fluctuations and the results were also in agreement with molecular dynamics simulations and normal mode analyses. Implications of the results for the drug-resistance engendered by mutations are discussed briefly. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A prospective study design was used to investigate the association between different degrees of fundus pigmentation and the indicence of retinopathy of prematurity (ROP) among very low birth weight infants in a large neonatal intensive care unit. METHODS: The study group consisted of 161 infants weighing 1500 g or less at birth and included all infants born from 1988 to 1990 who survived at least 10 weeks. Presence or lack of any acute stage ROP was determined by weekly ophthalmological examination from the age of 4 weeks. The degree of fundus pigmentation was recorded for each infant during the first examination. RESULTS: Infants with dark fundus pigmentation were found to be at half the risk of developing ROP as compared with infants having light/medium fundus pigmentation (relative risk = 0.5; 95% confidence interval = 0.2-1.1). When controlled for birth weight, gestational age, length of oxygen therapy, and ethnic group in multivariate analysis, dark pigmentation was an independent and statistically significant protective factor (odds ration = 0.09, 95% confidence interval = 0.02-0.06). None of the infants with Stage III ROP or higher had dark pigmentation. CONCLUSION: We speculate that large amounts of melanin in the retinal pigment epithelium or choroid may protect the dark-pigmented very low birth weight infant from developing ROP. [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]

F[sub 1]F[sub 0]-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 0] 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 β subunits (β[sub TP], β[sub DP], β[sub E]) observed in the crystal structures of the mitochondrial enzyme, MF[sub 1]. Using free energy difference simulations for the hydrolysis reaction ATP+H[sub 2]O → ADP+ Pi in the β[sub TP] and β[sub DP] sites and unisite hydrolysis data, we are able to identify β[sub TP] as the "tight" (K[sub D] = 10[sup -12] M, MF[sub 1]) binding site for ATP and β[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 β[sub TP] and β[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. [ABSTRACT FROM AUTHOR]