Characteristics of Ramachandran maps of L-alanine diamides as computed by various molecular mechanics, semiempirical and ab initio MO methods. A search for primary standard of peptide conformational stability

The optimized geometries and relative energies obtained by four force field and two semi-empirical methods were compared with ab initio results computed for formyl-L-alaninamide. Not all methods yielded the same number of minimum energy conformers. Furthermore, while the optimized geometries of the conformers found were comparable, the computed relative energies varied substantially. Also, the force field calculations produced Ramachandran maps that did not even have the appearance of the ab initio Ramachandran map. Correlating the ab initio relative energies (Delta E) or free energy (Delta G) with the log of relative populations, In(p(x)/p(gamma L)), led to linear relationships from which four conformers deviated; two of them (alpha(L) and epsilon(L)) were overly destabilized and two of them (gamma(L) and gamma(D)) were over-stabilized. It is suggested that, after such deviations are corrected, a primary standard may be obtained that might be useful in further investigations related to force-field parametrization as well as protein folding. (C) 1998 Elsevier Science B.V. All rights reserved

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

The response of plant community diversity to alien invasion: evidence from a sand dune time series

This study examines the process of invasion of coastal dunes in north-eastern Italy along a 60-year time series considering alien attributes (origin, residence time, invasive status, and growth form strategy) and habitat properties (species richness, diversity and evenness, proportion of aliens, and proportion of focal species). Vegetation changes through time were investigated in four sandy coastal habitats, using a fine-scale diachronic approach that compared vegetation data collected by use of the same procedure, in four time periods, from the 1950s to 2011. Our analysis revealed an overall significant decline of species richness over the last six decades. Further, both the average number of species per plot and the mean focal species proportion were proved to be negatively affected by the increasing proportion of alien species at plot level. The severity of the impact, however, was found to be determined by a combination of species attributes, habitat properties, and human disturbance suggesting that alien species should be referred to as ‘‘passengers’’ and not as ‘‘drivers’’ of ecosystem change. Passenger alien species are those which take advantage of disturbances or other changes to which they are adapted but that lead to a decline in native biodiversity. Their spread is facilitated by widespread anthropogenic environmental alterations, which create new, suitable habitats, and ensure human-assisted dispersal, reducing the distinctiveness of plant communities and inducing a process of biotic homogenization

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review.

Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Gram-positive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospital-acquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections