E. W. Prohofsky

Study of hydration of the Na+ ion using a polarizable water model

We report some results of applying a polarizable water model (the PE model) to the molecular dynamics simulation of hydrated Na+ ion microclusters Na+(H2O)n with n=1,...,6. We found that the PE model with just two adjustable parameters reproduces the experimental enthalpies of formation of the ion–water microclusters better than a number of other methods. We also found that for n=6 at 0 K the water molecules do not form a regular octahedron. This predicted change in structure appears to be in agreement with experimental observations.

Resonant and localized breathing modes in terminal regions of the DNA double helix

A Greens function approach is used in constructing a dynamic model of a semi-infinite length of the DNA homopolymer B poly(d) . poly(d). Considerable attention is focused on the hydrogen bond stretching close to the terminus. A melting (or breathing) coordinate (M) is defined as an average over the three linking hydrogen bond stretches in a unit cell. The thermal mean squared amplitude of (M) is enhanced at the chain end compared with the interior. Spectral branches at 69, 80 and 105 cm-1, as well as a local mode at 75 cm-1, are primary contributors to the enhancement. We suggest that this fact can affect the thermal melting of a DNA double helical homopolymer, enhancing the tendency to start from an end (if one is available). We show how certain infinite chain modes with small (M) amplitude can turn into breathing modes near the terminus, and suggest that the same phenomenon may occur near other specific base-pair sequences. There is also considerable attention paid to the low microwave region from approximately 0 to 1.75 cm-1. The thermally activated modes in this frequency region contribute approximately (0.02 A)2 to [M2(0)] at 40 K, approximately two orders of magnitude greater than for [M2(infinity)]. Most important however, is the existence of narrow resonant modes in this frequency region. Particularly pronounced resonances near 0.03 cm-1 and 0.08 cm-1 (approximately 0.9 and 2.4 GHz) amplify M2(0) at the terminus by about for orders of magnitude over the infinite chain value M2(infinity).

The normal vibrations of tetrahydrofuran and its deuterated derivatives

Abstract A normal co-ordinate analysis of the vibrations of tetrahydrofuran and several deuterated derivatives has been performed assuming the molecules possess C 2ν , symmetry. The method of damped least squares was used to obtain values for 30 force constants in a valence force field. This force field was defined in terms of a redundant set of 43 internal co-ordinates. The refinement waa performed using cartesian co-ordinates, so there was no attempt to eliminate the redundancies. Approximately 80 frequencies were reproduced with an average error of about 9 cm −1 .

Iron normal mode dynamics in (nitrosyl)iron(II)tetraphenylporphyrin from X-ray nuclear resonance data.

The complete iron atom vibrational spectrum has been obtained by refinement of normal mode calculations to nuclear inelastic x-ray absorption data from (nitrosyl)iron(II)tetraphenylporphyrin, FeTPP(NO), a useful model for heme dynamics in myoglobin and other heme proteins. Nuclear resonance vibrational spectroscopy (NRVS) provides a direct measurement of the frequency and iron amplitude for all normal modes involving significant displacement of (57)Fe. The NRVS measurements on isotopically enriched single crystals permit determination of heme in-plane and out-of-plane modes. Excellent agreement between the calculated and experimental values of frequency and iron amplitude for each mode is achieved by a force-field refinement. Significantly, we find that the presence of the phenyl groups and the NO ligand leads to substantial mixing of the porphyrin core modes. This first picture of the entire iron vibrational density of states for a porphyrin compound provides an improved model for the role of iron atom dynamics in the biological functioning of heme proteins.

A self‐consistent microscopic theory of hydrogen bond melting with application to poly(dG)⋅poly(dC)

In this paper we develop a modified self‐consistent phonon approximation model which displays effects which indicate melting. The model is applied to hydrogen bond melting of poly (dG)⋅poly(dC) and predicts melting at 340 K. The calculation has no parameters adjusted to fit the melting, the hydrogen bond potentials are adjusted to fit data at room temperature.

Premelting base pair opening probability and drug binding constant of a daunomycin-poly d(GCAT).poly d(ATGC) complex

We calculate room temperature thermal fluctuational base pair opening probability of a daunomycin-poly d(GCAT).poly d(ATGC) complex. This system is constructed at an atomic level of detail based on x-ray analysis of a crystal structure. The base pair opening probabilities are calculated from a modified self-consistent phonon approach of anharmonic lattice dynamics theory. We find that daunomycin binding substantially enhances the thermal stability of one of the base pairs adjacent the drug because of strong hydrogen bonding between the drug and the base. The possible effect of this enhanced stability on the drug inhibition of DNA transcription and replication is discussed. We also calculate the probability of drug dissociation from the helix based on the selfconsistent calculation of the probability of the disruption of drug-base H-bonds and the unstacking probability of the drug. The calculations can be used to determine the equilibrium drug binding constant which is found to be in good agreement with observations on similar daunomycin-DNA systems.

Energy flow considerations and thermal fluctuational opening of DNA base pairs at a replicating fork : unwinding consistent with observed replication rates

The effect of an open loop of various sizes on the thermal stability of the adjoining intact base pairs in a duplex DNA chain is studied in a lattice model of Poly(dG).Poly(dC). We find that for a Y-shaped fork configuration the thermal fluctuation at the fork is so enhanced that the life time of the adjoining base pair is much smaller than the 1 millisecond time scale associated with helicase separation of a base pair in some systems. Our analysis indicates that thermal fluctuational base pair opening may be of importance in facilitating the enzyme unwinding process during chain elongation of a replicating DNA. It is most likely that the thermal fluctuational opening of the base pair at the junction of a replicating fork is fast enough so that a DNA unwinding enzyme can encounter an unstacked base pair with reasonable probability. This conclusion can explain several experimental observations regarding the temporal relationship between ATP hydrolysis by accessory proteins and primer elongation by a holoenzyme complex in ssDNA. We also discuss a mechanism by which the energy associated with ATP hydrolysis may enhance the thermal driven base opening mechanism.

Synergistic effects in the melting of DNA hydration shell: melting of the minor groove hydration spine in poly(dA).poly(dT) and its effect on base pair stability

We propose that water of hydration in contact with the double helix can exist in several states. One state, found in the narrow groove of poly(dA).poly(dT), should be considered as frozen to the helix, i.e., an integral part of the double helix. We find that this enhanced helix greatly effects the stability of that helix against base separation melting. Most water surrounding the helix is, however, melted or disassociated with respect to being an integral part of helix and plays a much less significant role in stabilizing the helix dynamically, although these water molecules play an important role in stabilizing the helix conformation statically. We study the temperature dependence of the melting of the hydration spine and find that narrow groove nonbonded interactions are necessary to stabilize the spine above room temperature and to show the broad transition observed experimentally. This calculation requires that synergistic effects of nonbonded interactions between DNA and its hydration shell affect the state of water-base atom hydrogen bonds. The attraction of waters into narrow groove tends to retain waters in the groove and compress or strain these hydrogen bonds.

A molecular dynamics study of water microclusters surrounding a phosphate ion

Molecular dynamics calculations similar to those developed for pure water by Rahman and Stillinger have been carried out for clusters of PO43−(H2O)n, where n = 6, 12, and 18. It was found that the water molecules are distributed in one, two, and three hydration shells in the n = 6, n = 12, and n = 18 clusters, respectively. There is exchange of water molecules between the hydration shells. The density profile and the velocity autocorrelation functions of the hydrogen and oxygen atoms of the water molecules are reported. For the n = 6 cluster and the first hydration shell of the n = 12 cluster the velocities of the hydrogen and oxygen atoms of the water molecules are resolved into three components in accordance with the symmetry of the phosphate ion. The autocorrelation functions of these velocity components exhibit simple time dependences.

Displacements of backbone vibrational modes of A-DNA and B-DNA

We display the displacement vectors or eigenvectors of calculations of the A- and B-DNA backbones. These calculations are based on a refinement scheme that simultaneously fit several backbone modes of A-DNA, B-DNA, and A-RNA. We discuss the role of symmetry operations in mode calculations and the relevance of these displacement vectors to the interpretation of linear dichroism measurements performed on the A- and B-DNA helix.