Strong covalent bonding between two graphene layers

We show that two graphene layers stacked directly on top of each other (AA stacking) form strong chemical bonds when the distance between planes is 0.156 nm. Simultaneously, C-C in-plane bonds are considerably weakened from partial double-bond (0.141 nm) to single bond (0.154 nm). This polymorphic form of graphene bilayer is meta-stable w.r.t. the one bound by van der Waals forces at a larger separation (0.335 nm) with an activation energy of 0.16 eV/cell. Similarly to the structure found in hexaprismane, C forms four single bonds in a geometry mixing 90^{0} and 120^{0} angles. Intermediate separations between layers can be stabilized under external anisotropic stresses showing a rich electronic structure changing from semimetal at van der Waals distance, to metal when compressed, to wide gap semiconductor at the meta-stable minimum.Comment: tar gzip latex 4 pages 4 figure

Introduction to protein folding for physicists

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the conformational behaviour of flexible molecules is nothing more than a complex physical problem, increasingly more physicists are moving into the study of protein systems, bringing with them powerful mathematical and computational tools, as well as the sharp intuition and deep images inherent to the physics discipline. This work attempts to facilitate the first steps of such a transition. In order to achieve this goal, we provide an exhaustive account of the reasons underlying the protein folding problem enormous relevance and summarize the present-day status of the methods aimed to solving it. We also provide an introduction to the particular structure of these biological heteropolymers, and we physically define the problem stating the assumptions behind this (commonly implicit) definition. Finally, we review the 'special flavor' of statistical mechanics that is typically used to study the astronomically large phase spaces of macromolecules. Throughout the whole work, much material that is found scattered in the literature has been put together here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co

Angular Forces Around Transition Metals in Biomolecules

Quantum-mechanical analysis based on an exact sum rule is used to extract an semiclassical angle-dependent energy function for transition metal ions in biomolecules. The angular dependence is simple but different from existing classical potentials. Comparison of predicted energies with a computer-generated database shows that the semiclassical energy function is remarkably accurate, and that its angular dependence is optimal.Comment: Tex file plus 4 postscript figure

A Bayesian test for the appropriateness of a model in the biomagnetic inverse problem

This paper extends the work of Clarke [1] on the Bayesian foundations of the biomagnetic inverse problem. It derives expressions for the expectation and variance of the a posteriori source current probability distribution given a prior source current probability distribution, a source space weight function and a data set. The calculation of the variance enables the construction of a Bayesian test for the appropriateness of any source model that is chosen as the a priori infomation. The test is illustrated using both simulated (multi-dipole) data and the results of a study of early latency processing of images of human faces. [1] C.J.S. Clarke. Error estimates in the biomagnetic inverse problem. Inverse Problems, 10:77--86, 1994.Comment: 13 pages, 16 figures. Submitted to Inverse Problem

To hit or not to hit, that is the question -genome-wide structure-based druggability predictions for <i>pseudomonas aeruginosa </i>proteins

Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa

Multiple configurations of N-methylpyrrole binding on Si(111)-7×7

The adsorption configurations of N-methylpyrrole on Si(111)-7×7 were investigated using high-resolution electron energy-loss spectroscopy, x-ray photoelectron spectroscopy (XPS), scanning tunneling microscopy (STM), and density function theory calculations. Compared to physisorbed N-methylpyrrole, chemisorbed molecules present a different vibrational feature at 2886 cm-1 attributable to ν[(Si)Csp3-H] in addition to the vibrational features of (sp2)Cα-H (3106 cm-1), (sp2)Cβ-H (3050 cm-1), and C—H of CH3 (2944 cm-1) stretching modes, demonstrating the direct interaction between C=C bonds and Si(111)-7×7. The major change of N 1s XPS spectrum of N-methylpyrrole upon chemisorption strongly suggests the coexistence of two chemisorption states, further confirmed in the strong dependence of STM image features on the sample bias together with statistical analysis. The concurrent occurrence of [4+2] and [2+2] cycloadditions is proposed to account for these two adsorption configurations of N-methylpyrrole on Si(111)-7×

Top-Down Feedback in an HMAX-Like Cortical Model of Object Perception Based on Hierarchical Bayesian Networks and Belief Propagation

PubMed ID: 2313976

Актуальність впровадження систем газового обліку в сучасних умовах

Free energy calculation has long been an important goal for molecular dynamics simulation and force field development, but historically it has been challenged by limited performance, accuracy, and creation of topologies for arbitrary small molecules. This has made it difficult to systematically compare different sets of parameters to improve existing force fields, but in the past few years several authors have developed increasingly automated procedures to generate parameters for force fields such as Amber, CHARMM, and OPLS. Here, we present a new framework that enables fully automated generation of GROMACS topologies for any of these force fields and an automated setup for parallel adaptive optimization of high-throughput free energy calculation by adjusting lambda point placement on the fly. As a small example of this automated pipeline, we have calculated solvation free energies of 50 different small molecules using the GAFF, OPLS-AA, and CGenFF force fields and four different water models, and by including the often neglected polarization costs, we show that the common charge models are somewhat underpolarized.QC 20150505</p

Erratum to: Molecular modelling study of 2-phenylethynyladenosine (PEAdo) derivatives as highly selective A3 adenosine receptor ligands

A series of 2-phenylethynyladenosine (PEAdo) derivatives substituted in the N6- and 4′position was synthesised and the new derivatives were tested at the four human adenosine receptors stably transfected into Chinese hamster ovary (CHO) cells, using radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assay (A2B). Binding studies showed that the presence of a phenyl ethynyl group in the 2 position of adenosine favoured the interaction with A3 receptors, resulting in compounds endowed with high affinity and selectivity for the A3 subtype. Additional substitution of the N6- and 4′position increases both A3 affinity and selectivity. The results showed that the new compounds have a good affinity for the A3 receptor and in particular, the N6-methoxy-2-phenylethynyl-5′N-methylcarboxamidoadenosine, with a Ki at A3 of 1.9 nM and a selectivity A1/A3 and A2A/A3 of 4,800- and 8,600-fold, respectively. Therefore, it is one of the most potent and selective agonists at the human A3 adenosine receptor subtype reported so far. Furthermore, functional assays of inhibition of 10 μM forskolin-stimulated cAMP production via the adenosine A3 receptor revealed that the new trisubstituted adenosine derivatives behave as full agonist of this receptor subtype. Docking analysis of these compounds was performed at a homology model of the human A3 receptor based on the bovine rhodopsin crystal structure as template, and the results are in accordance with the biological data

Foldamers of β-peptides : conformational preference of peptides formed by rigid building blocks : The first MI-IR spectra of a triamide nanosystem

To determine local chirality driven conformational preferences of small aminocyclobutane-1-carboxylic acid derivatives, X-(ACBA) n -Y, their matrix-isolation IR spectra were recorded and analyzed. For the very first time model systems of this kind were deposited in a frozen (~10 K) noble gas matrix to reduce line width and thus, the recorded sharp vibrational lines were analyzed in details. For cis-(S,R)-1 monomer two “zigzag” conformers composed of either a six or an eight-membered H-bonded pseudo ring was identified. For trans-(S,S)-2 stereoisomer a zigzag of an eight-membered pseudo ring and a helical building unit were determined. Both findings are fully consistent with our computational results, even though the relative conformational ratios were found to vary with respect to measurements. For the dimers (S,R,S,S)-3 and (S,S,S,R)-4 as many as four different cis,trans and three different trans,cis conformers were localized in their matrix-isolation IR (MI-IR) spectra. These foldamers not only agree with the previous computational and NMR results, but also unambiguously show for the first time the presence of a structure made of a cis,trans conformer which links a “zigzag” and a helical foldamer via a bifurcated H-bond. The present work underlines the importance of MI-IR spectroscopy, applied for the first time for triamides to analyze the conformational pool of small biomolecules. We have shown that the local chirality of a β-amino acid can fully control its backbone folding preferences. Unlike proteogenic α-peptides, β- and especially (ACBA) n type oligopeptides could thus be used to rationally design and influence foldamer’s structural preferences