Influence of the charge state on the structures and interactions of vancomycin antibiotics with cell-wall analogue peptides: experimental and theoretical studies.

Charge matters! The charge state significantly influences the conformation and the binding energy between vancomycin antibiotic and bacterial cell-wall analogue peptides (see figure). Surface-induced dissociation (SID) studies provide a quantitative comparison between the stabilities of different charge states of the complex.In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the noncovalent complex between the vancomycin and the cell-wall peptide analogue N(alpha),N(epsilon)-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac(2)LKdAdA).

Experimental and theoretical studies of the structures and interactions of vancomycin antibiotics with cell wall analogues.

Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (N(alpha),N(epsilon)-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy-resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Molecular dynamics simulations of the vancomycin, peptide, and vancomycin-peptide complex were carried out to explore the low energy conformations.

Computer simulation of uranyl uptake by the rough lipopolysaccharide membrane of Pseudomonas aeruginosa.

Heavy metal environmental contaminants cannot be destroyed but require containment, preferably in concentrated form, in a solid or immobile form for recycling or final disposal. Microorganisms are able to take up and deposit high levels of contaminant metals, including radioactive metals such as uranium and plutonium, into their cell wall. Consequently, these microbial systems are of great interest as the basis for potential environmental bioremediation technologies.

Computational investigation and hydrogen/deuterium exchange of the fixed charge derivative tris(2,4,6-trimethoxyphenyl) phosphonium: implications for the aspartic acid cleavage mechanism.

Aspartic acid (Asp)-containing peptides with the fixed charge derivative tris(2,4,6trimethoxyphenyl) phosphonium (tTMP-P+) were explored computationally and experimentally by hydrogen/deuterium (H/D) exchange and by fragmentation studies to probe the phenomenon of selective cleavage C-terminal to Asp in the absence of a "mobile" proton. Ab initio modeling of the tTMP-P+ electrostatic potential shows that the positive charge is distributed on the phosphonium group and therefore is not initiating or directing fragmentation as would a "mobile" proton. Geometry optimizations and vibrational analyses of different Asp conformations show that the Asp structure with a hydrogen bond between the side-chain hydroxy and backbone carbonyl lies 2.

Direct experimental observation of the low ionization potentials of guanine in free oligonucleotides by using photoelectron spectroscopy.

Photodetachment photoelectron spectroscopy is used to probe the electronic structure of mono-, di-, and trinucleotide anions in the gas phase. A weak and well defined threshold band was observed in the photoelectron spectrum of 2'-deoxyguanosine 5'-monophosphate at a much lower ionization energy than the other three mononucleotides. Density function theory calculations revealed that this unique spectral feature is caused by electron-detachment from a pi orbital of the guanine base on 2'-deoxyguanosine 5'-monophosphate, whereas the lowest ionization channel for the other three mononucleotides takes place from the phosphate group.

Characterization of electronic structure and properties of a Bis(histidine) heme model complex.

Ferric and ferrous hemes, such as those present in electron transfer proteins, often have low-lying spin states that are very close in energy. To explore the relationship between spin state, geometry, and cytochrome electron transfer, we investigate, using density functional theory, the relative energies, electronic structure, and optimized geometries for a high- and low-spin ferric and ferrous heme model complex. Our model consists of an iron-porphyrin axially ligated by two imidazoles, which model the interaction of a heme with histidine residues.