Search

In order to investigate conformational preferences of the 21-residue peptide hormone endothelin-1 (ET-1), an extensive conformational search was carried out in vacuo using a combination of high temperature molecular dynamics/annealing and a Monte Carlo/minimization search in torsion angle space. Fully minimized conformations from the search were grouped into families using a clustering technique based on rms fitting over the Cartesian coordinates of the atoms of the peptide backbone of the ring region. A wide range of local energy mining were identified even though two disulfide bridges (Cys1-Cys15 and Cys3-Cys11) constrain the structure of the peptide. Low energy conformers of ET-1 as a nonionized species in vacuo are stabilized by intramolecular interaction of the ring region (residues 1-15) with the tail (residues 16-21). Strained conformations for individual residues are observed. Conformational similarity to protein loops is established by matching to protein crystal structures. In order to assess the influence of aqueous environment on conformational preference, the electrostatic contribution to the solvation energy was calculated for ET-1 as a fully ionized species (Asp8, Lys9, Glu10, Asp18, N- and C-terminus) using a continuum electrostatics model (DelPhi) for each of the conformers generated in vacuo, and the total solvation free energy was estimated by adding a hydrophobic contribution proportional to solvent accessible surface area. Solvation dramatically alters the relative energetics of ET-1 conformers from that calculated in vacuo. Conformers of ET-1 favored by the electrostatic solvation energy in water include conformers with helical secondary structure in the region of residues 9-15. Perhaps of most importance, it was demonstrated that the contribution to solvation by an individual charge depends not only on its solvent accessibility but on the proximity of other charges, i.e., it is a cooperative effect. This was shown by the calculation of electrostatic solvation energy as a function of conformation with individual charges systematically turned "on" and "off". The cooperative effect of multiple charges on solvation demonstrated in this manner calls into question models that relate solvation energy simply to solvent accessibility by atom or residue alone.

For molecular mechanics simulations of solvated molecules, it is important to use a consistent approach for calculating both the force field energy and the solvation free energy. A continuum solvation model based upon the atomic charges provided with the CFF91 force field is derived. The electrostatic component of the solvation free energy is described by the Poisson-Bolzmann equation while the nonpolar comonent of the solvation energy is assumed to be proportional to the solvent accessible surface area of the solute. Solute atomic radii used to describe the interface between the solute and solvent are fitted to reproduce the energies of small organic molecules. Data for 140 compounds are presented and compared to experiment and to the results from the well-characterized quantum mechanical solvation model AM1-SM2. In particular, accurate results are obtained for amino acid neutral analogues (mean unsigned error of 0.3 kcal/mol). The conformational energetics of the solvated alanine dipeptide is d...

A continuum hydration model based upon the atomic charges provided with the CFF91 force field [A. B. Schmidt and R. M. Fine (1994) Molecular Simulation, 13. 347–365] has been extended to the octanol–water transfer. The electrostatic component of the transfer free energy is calculated using the finite-difference solution to the Poisson–Boltzmann equation while the nonpolar contributions are assumed to be proportional to the solute-excluded volume in water. All atomic charges and radii besides the aromatic carbon radius are equal in both solvents. The octanol dielectric constant and the probe radius are the main fitting parameters defining the octanol phase. The model has been tested for 38 organic molecules related to the amino acid residues and generally provides a high accuracy. In particular, the mean unsigned error for N-acetyl amino acid amides is 0.5 kcal/mol. © 1995 John Wiley & Sons, Inc.

We have studied muon-produced hadrons from a deuterium target. The structure functions and the charge ratios are reported for neutrons; the transverse momentum and azimuthal distributions are reported for deuterons. The structure function for the neutron is similar to that of the proton. The charge ratio of produced hadrons follows the expectation of a simple spin-1/2 quark model. Transverse-momentum results agree with those at lower energy and are similar to those from hadron--hadron interactions. No azimuthal anisotropy is seen. (AIP)

Inclusive hadron production in muon-proton inelastic scattering has been measured for ${q}^{2}g0.5$ ${(\mathrm{G}\mathrm{e}\mathrm{V}/\mathit{c})}^{2}$ and $10l\ensuremath{\nu}l135$ GeV. The results are presented in the form of the transverse momentum distribution of charged hadrons and the hadron invariant structure function $F({x}^{\ensuremath{'}})$. Results are given for different regions of ${q}^{2}$ and $s$.

This paper reports measurements of the hadrons produced in the inelastic scattering of 147-GeV muons by protons and deuterons in an experiment carried out at Fermi National Accelerator Laboratory. Both the scattered muon and the hadrons were measured in a large spectrometer. Properties of the hadron spectra are presented for proton, deuteron, and neutron targets and compared with theoretical models and with hadron spectra from related processes. Emphasis is placed on the quark-parton model and the data are found to be in substantial agreement with it. The average transverse momentum of the hadrons with respect to the virtual photon direction shows no dependence on the muon scattering variables. The data display "jet behavior" of the inclusive hadrons comparable to that found in ${e}^{+}{e}^{\ensuremath{-}}$ annihilations.

We have studied the production of $\ensuremath{\rho}$ and $\ensuremath{\varphi}$ mesons from muon scattering on a liquidhydrogen target at 150 and 100 GeV. For the $\ensuremath{\rho}$ we observe a skewed mass distribution which becomes somewhat more normal with increasing ${Q}^{2}$ (the square of the four-momentum transferred from the muon), and an exponential distribution in $t$ (the square of the four-momentum transferred to the target proton) with a slope which is consistent with a slight decrease as ${Q}^{2}$ increases. The dependence of the cross section on ${Q}^{2}$ follows that of the square of the $\ensuremath{\rho}$ propagator with little contribution from longitudinal $\ensuremath{\rho}$ production. The angular distribution of the $\ensuremath{\rho}$ decay confirms the smallness of the contribution from longitudinal $\ensuremath{\rho}$ production at our energies. The cross section when extrapolated to ${Q}^{2}=0$ agrees with that measured in real photoproduction. The decay angular distribution of the $\ensuremath{\rho}$ decay shows that $s$-channel helicity is largely conserved, although we detect a helicity-single-flip contribution at the 10-15% level. Natural-parity exchange in the $t$ channel dominates, and the transverse and longitudinal amplitudes are found to be in phase. These characteristics are consistent with the diffractive nature of the vectordominance model. The $t$ distribution of $\ensuremath{\varphi}$ production is also exponential, although less steep than that for the $\ensuremath{\rho}$. We observe an elastically produced four-pion state at a mass of approximately 1600 MeV. We identify this state with the ${\ensuremath{\rho}}^{\ensuremath{'}}(1600)$, and find it to be produced with a distribution exponential in $t$.

Results on the nucleon structure function, $\ensuremath{\nu}{W}_{2}$, are presented for $0.2l~{q}^{2}l~50$ ${(\mathrm{G}\mathrm{e}\mathrm{V}/\mathit{c})}^{2}$ and $5l~\ensuremath{\nu}l~130$ GeV. They were obtained by scattering 147-GeV positive muons inelastically from a liquid deuterium target.

Measurements have been made of the inclusive scattering of 96, 147, and 219 GeV muons from hydrogen, and of 147 GeV muons from deuterium. Results are presented for the nucleon structure function F/sub 2/(x,Q/sup 2/) (equivalent..nu..W/sub 2/(x,Q/sup 2/)) for 10 < ..nu.. < 200 GeV and 0.2 < Q/sup 2/ < 80 GeV/sup 2/. The value of F/sub 2/ rises with Q/sup 2/ at small x, and falls with Q/sup 2/ at large x, in agreement with the ideas of quantum chromodynamics. An average value of the ratio sigma/sub L//sigma/sub T/ equivalent R = 0.52 +- 0.35 has been obtained for the region 0.003 < x < 0.10 and 0.4 < Q/sup 2/ < 30 GeV/sup 2/. The values of F/sub 2/ from this experiment have been combined with those from other charged-lepton scattering experiments to determine moments of the structure functions. The variation with Q/sup 2/ of these moments is used to derive values for ..lambda.., taking into account corrections up to second order in ..cap alpha../sub s/. The fit to the data is very good.

Cross sections for diffractive rho muoproduction in hydrogen are presented for 90 GeV

Results on the proton structure function, $\ensuremath{\nu}{W}_{2}$ are presented for $0.3l{q}^{2}l50$ Ge${\mathrm{V}}^{2}$ and $5l\ensuremath{\nu}l130$ GeV. They are compared to earlier data and displayed to demonstrate violations of scaling. Values are reported for the energy-momentum sum rule and for $R\ensuremath{\equiv}\frac{{\ensuremath{\sigma}}_{L}}{{\ensuremath{\sigma}}_{T}}$ over a limited kinematic region.

We have observed coherent production of $\ensuremath{\rho}$ mesons by muon scattering on carbon. The differential cross section falls steeply with increasing $t$ (the square of the four-momentum transferred to the nucleus) and helicity is conserved in the $s$ channel. Dominance by coherent production, as well as the radius of the carbon nucleus and the total $\ensuremath{\rho}$-nucleus cross section derived from our measurements, are consistent with what is observed in other related processes.

Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites.