No abstract

No abstract

The heterodimeric antimicrobial peptide distinctin is composed of 2 linear peptide chains of 22-and 25-aa residues that are connected by a single intermolecular S-S bond. This heterodimer has been considered to be a unique example of a previously unrecorded class of bioactive peptides. Here the 2 distinctin chains were prepared by chemical peptide synthesis in quantitative amounts and labeled with 15 N, as well as 15 N and 2 H, at selected residues, respectively, and the heterodimer was formed by oxidation. CD spectroscopy indicates a high content of helical secondary structures when associated with POPC/POPG 3:1 vesicles or in membrane-mimetic environments. The propensity for helix formation follows the order heterodimer >chain 2 >chain 1, suggesting that peptidepeptide and peptide-lipid interactions both help in stabilizing this secondary structure. In a subsequent step the peptides were reconstituted into oriented phospholipid bilayers and investigated by 2 H and proton-decoupled 15 N solid-state NMR spectroscopy. Whereas chain 2 stably inserts into the membrane at orientations close to perfectly parallel to the membrane surface in the presence or absence of chain 1, the latter adopts a more tilted alignment, which further increases in the heterodimer. The data suggest that membrane interactions result in considerable conformational rearrangements of the heterodimer. Therefore, chain 2 stably anchors the heterodimer in the membrane, whereas chain 1 interacts more loosely with the bilayer. These structural observations are consistent with the antimicrobial activities when the individual chains are compared to the dimer. amphipathic alpha-helix ͉ membrane insertion ͉ membrane protein structure determination ͉ peptide-peptide interactions ͉ synergistic activity A s more and more pathogens develop resistance against many commonly used antibiotics, urgent actions are needed to counteract this resistance and new bactericidal and fungicidal compounds have to be developed. Both plants and animals produce, store, and secrete antibiotic peptides in exposed tissues, or synthesize such compounds upon induction, and indeed many antibiotic peptides have been isolated from natural sources (1, 2). The availability of these molecules establishes a defense system that can be set into action immediately when infections occur, and several antimicrobial peptides have been found to also exhibit virucidal and tumorcidal activities (reviewed in refs. 3 and 4). The lack of sequence homology, the activity of chiral analogues, the amphipathic properties, and biophysical measurements all suggest that the bacterial membranes rather than chiral receptors are the targets of many of these peptides (1, 3), although more recent findings suggest that at least some of them also have internal targets after crossing the membrane (5, 6).The heterodimeric peptide distinctin has been isolated from Phyllomedusa distincta, a frog living in the southeast Atlantic forests of Brazil (7). The distinctin is composed of 2 linear peptide chains, one of 22-an...

We present multiconfigurational self-consistent reaction field theory and implementation for solvent effects on a solute molecular system that is not in equilibrium with the outer solvent. The approach incorporates two different polarization vectors for studying the influence of the solvent. The solute, an atom, a molecule or a supermolecule, is assumed to be surrounded by a linear, homogeneous medium described by two polarization vector fields, the optical polarization vector and the inertial polarization vector fields. The optical polarization vector is always in equilibrium with the actual electronic structure whereas the inertial polarization vector is not necessarily in equilibrium with the actual electronic structure. The electronic structure of the compound is described by a correlated electronic wave function—a multiconfigurational self-consistent field (MCSCF) wave function. This wave function is fully optimized with respect to all variational parameters in the presence of the surrounding polarizable dielectric medium having two distinct polarization vectors. We develop from a compact and simple expression a direct and second-order convergent optimization procedure for the solvent states influenced by the two types of polarization vectors. The general treatment of the correlation problem through the use of complete and restricted active space methodologies makes the present multiconfigurational self-consistent reaction field approach general in that it can handle any type of state, open-shell, excited, and transition states. We demonstrate the theory by computing solvatochromatic shifts in optical/UV spectra of some small molecules and electron ionization and electron detachment energies of the benzene molecule. It is shown that the dependency of the solvent induced affinity in benzene is nonmonotonic with respect the optical dielectric constant if inertial polarization effects also are accounted for.

We have performed Car-Parrinello molecular dynamics simulations at ambient conditions for four-, five- and six-coordinated Cu(II) aqua complexes. The molecular geometry has been investigated in terms of Cu-O, Cu-H bond lengths and O-Cu-O bond angles and compared with earlier experimental measurement results and theoretical calculations. We find that the average Cu-O and Cu-H bond lengths increase with increasing coordination number. We have also observed relatively faster structural transition in the case of five-coordinated complex between trigonal bipyramidal and square pyramidal geometry. This result deviates from the findings of the earlier report (A. Pasquarello et al., Science, 2001, 291, 856) on copper(II) in aqueous solution and we attribute these differences to the neglect of solvent environment in our calculations. The averaged absorption spectra for the copper(II) aqua complexes have been computed using spin-restricted density functional linear response formalism taking 100 snap shots from a trajectory of 0.48 ps. We find that the calculated spectra are significantly different, showing clear features that distinguish each coordination model. Comparison with the experimentally reported absorption spectra is made wherever it is possible and the results obtained favor the distorted fivefold-coordination arrangement for the molecular structure of the Cu(II) ion in aqueous solution.