Atomistic simulations of isotactic poly(methyl methacrylate) melts: Exploring the backbone conformation

Molecular dynamics simulations were performed separately on an isotactic poly(methyl methacrylate) (PMMA) melt and on an atactic PMMA melt. These simulations allow for a detailed atomistic exploration of the conformational space about the polymers' backbone at a temperature above the glass transition for both polymers, which is experimentally difficult to accomplish. In agreement with previous experimental and theoretical studies, we found the trans-trans backbone conformation to be the most energetically stable, followed by the trans-gauche conformations. Unique in this study is the ability to attribute how the underlying meso and racemic diad pairs contribute to the overall backbone population. Additional simulations were performed on methyl methacrylate, the compound that forms PMMA through radical reactions. These latter simulations help to validate our recently created force field for use in condensed-phase simulations

Structure and thermodynamics of H3O+(H2O)8 clusters: A combined molecular dynamics and quantum mechanics approach

We have studied the structure and stability of H3O+(H2O)8 clusters using a combination of molecular dynamics sampling and high-level ab initio calculations. 20 distinct oxygen frameworks are found within 2 kcal/mol of the electronic or standard Gibbs free energy minimum. The impact of quantum zero-point vibrational corrections on the relative stability of these isomers is quite significant. The box-like isomers are favored in terms of electronic energy, but with the inclusion of zero-point vibrational corrections and entropic effects tree-like isomers are favored at higher temperatures. Under conditions from 0 to 298.15 K, the global minimum is predicted to be a tree-like structure with one dangling singly coordinated water molecule. Above 298.15 K, higher entropy tree-like isomers with two or more singly coordinated water molecules are favored. These assignments are generally consistent with experimental IR spectra of (H3O+)(H2O)8 obtained at 150 K

Optimized atomistic force fields for aqueous solutions of Magnesium and Calcium Chloride: Analysis, achievements and limitations

Molecular simulations are an important tool in the study of aqueous salt solutions. To predict the physical properties accurately and reliably, the molecular models must be tailored to reproduce experimental data. In this work, a combination of recent global and local optimization tools is used to derive force fields for MgCl2 (aq) and CaCl2 (aq). The molecular models for the ions are based on a Lennard-Jones (LJ) potential with a superimposed point charge. The LJ parameters are adjusted to reproduce the bulk density and shear viscosity of the different solutions at 1 bar and temperatures of 293.15, 303.15, and 318.15 K. It is shown that the σ-value of chloride consistently has the strongest influence on the system properties. The optimized force field for MgCl2 (aq) provides both properties in good agreement with the experimental data over a wide range of salt concentrations. For CaCl2 (aq), a compromise was made between the bulk density and shear viscosity, since reproducing the two properties requires two different choices of the LJ parameters. This is demonstrated by studying metamodels of the simulated data, which are generated to visualize the correlation between the parameters and observables by using projection plots. Consequently, in order to derive a transferable force field, an error of ∼3% on the bulk density has to be tolerated to yield the shear viscosity in satisfactory agreement with experimental data

Antiestrogenic and anticancer activities of peptides derived from the active site of alpha-fetoprotein

Cyclo{\{}[{\}}EKTOVNOGN] (AFPep), a cyclic 9-amino acid peptide derived from the active site of alpha-fetoprotein, has been shown to prevent carcinogen-induced mammary cancer in rats and inhibit the growth of ER(+) human breast cancer xenografts in mice. Recently, studies using replica exchange molecular dynamics predicted that the TOVN region of AFPep might form a dynamically stable putative Type I beta-turn, and thus be biologically active without additional amino acids. The studies presented in this paper were performed to determine whether TOVN and other small analogs of AFPep would inhibit estrogen-stimulated cancer growth and exhibit a broad effective-dose range. These peptides contained nine or fewer amino acids, and were designed to bracket or include the putative pharmacophoric region (TOVN) of AFPep. Biological activities of these peptides were evaluated using an immature mouse uterine growth inhibition assay, a T47D breast cancer cell proliferation assay, and an MCF-7 breast cancer xenograft assay. TOVN had very weak antiestrogenic activity in comparison to AFPep\u27s activity, whereas TOVNO had antiestrogenic and anticancer activities similar to AFPep. OVNO, which does not form a putative Type I beta-turn, had virtually no antiestrogenic and anticancer activities. A putative proteolytic cleavage product of AFPep, TOVNOGNEK, significantly inhibited E(2)-stimulated growth in vivo and in vitro over a wider dose range than AFPep or TOVNO. We conclude that TOVNO has anticancer potential, that TOVNOGNEK is as effective as AFPep in suppressing growth of human breast cancer cells, and that it does so over a broader effective-dose range