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

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

Open Babel: An open chemical toolbox

Background: A frequent problem in computational modeling is the interconversion of chemical structures between different formats. While standard interchange formats exist (for example, Chemical Markup Language) and de facto standards have arisen (for example, SMILES format), the need to interconvert formats is a continuing problem due to the multitude of different application areas for chemistry data, differences in the data stored by different formats (0D versus 3D, for example), and competition between software along with a lack of vendorneutral formats. Results: We discuss, for the first time, Open Babel, an open-source chemical toolbox that speaks the many languages of chemical data. Open Babel version 2.3 interconverts over 110 formats. The need to represent such a wide variety of chemical and molecular data requires a library that implements a wide range of cheminformatics algorithms, from partial charge assignment and aromaticity detection, to bond order perception and canonicalization. We detail the implementation of Open Babel, describe key advances in the 2.3 release, and outline a variety of uses both in terms of software products and scientific research, including applications far beyond simple format interconversion. Conclusions: Open Babel presents a solution to the proliferation of multiple chemical file formats. In addition, it provides a variety of useful utilities from conformer searching and 2D depiction, to filtering, batch conversion, and substructure and similarity searching. For developers, it can be used as a programming library to handle chemical data in areas such as organic chemistry, drug design, materials science, and computational chemistry. It is freely available under an open-source license fro

Training a Scoring Function for the Alignment of Small Molecules

A comprehensive data set of aligned ligands with highly similar binding pockets from the Protein Data Bank has been built. Based on this data set, a scoring function for recognizing good alignment poses for small molecules has been developed. This function is based on atoms and hydrogen-bond projected features. The concept is simply that atoms and features of a similar type (hydrogen-bond acceptors/donors and hydrophobic) tend to occupy the same space in a binding pocket and atoms of incompatible types often tend to avoid the same space. Comparison with some recently published results of small molecule alignments shows that the current scoring function can lead to performance better than those of several existing methods

Fast automated placement of polar hydrogen atoms in protein-ligand complexes

<p>Abstract</p> <p>Background</p> <p>Hydrogen bonds play a major role in the stabilization of protein-ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side-chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted.</p> <p>Results</p> <p>We have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein-ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach.</p> <p>Conclusion</p> <p>Our results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation.</p

Common cortical responses evoked by appearance, disappearance and change of the human face

<p>Abstract</p> <p>Background</p> <p>To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset), disappearance (Offset), and change (Change) using magnetoencephalography.</p> <p>Results</p> <p>Activity in and around the primary visual cortex (V1/V2) showed luminance-dependent behavior. Any of the three events evoked activity in the middle occipital gyrus (MOG) at 150 ms and temporo-parietal junction (TPJ) at 250 ms after the onset of each event. Onset and Change activated the fusiform gyrus (FG), while Offset did not. This FG activation showed a triphasic waveform, consistent with results of intracranial recordings in humans.</p> <p>Conclusion</p> <p>Analysis employed in this study successfully segregated four different elements involved in the spatio-temporal dynamics of cortical activations in response to a face stimulus. The results show the responses of MOG and TPJ to be associated with non-specific processes, such as the detection of abrupt changes or exogenous attention. Activity in FG corresponds to a face-specific response recorded by intracranial studies, and that in V1/V2 is related to a change in luminance.</p

Average and extreme multi-atom Van der Waals interactions: Strong coupling of multi-atom Van der Waals interactions with covalent bonding

<p>Abstract</p> <p>Background</p> <p>The prediction of ligand binding or protein structure requires very accurate force field potentials – even small errors in force field potentials can make a 'wrong' structure (from the billions possible) more stable than the single, 'correct' one. However, despite huge efforts to optimize them, currently-used all-atom force fields are still not able, in a vast majority of cases, even to keep a protein molecule in its native conformation in the course of molecular dynamics simulations or to bring an approximate, homology-based model of protein structure closer to its native conformation.</p> <p>Results</p> <p>A strict analysis shows that a specific coupling of multi-atom Van der Waals interactions with covalent bonding can, in extreme cases, increase (or decrease) the interaction energy by about 20–40% at certain angles between the direction of interaction and the covalent bond. It is also shown that on average multi-body effects decrease the total Van der Waals energy in proportion to the square root of the electronic component of dielectric permittivity corresponding to dipole-dipole interactions at small distances, where Van der Waals interactions take place.</p> <p>Conclusion</p> <p>The study shows that currently-ignored multi-atom Van der Waals interactions can, in certain instances, lead to significant energy effects, comparable to those caused by the replacement of atoms (for instance, C by N) in conventional pairwise Van der Waals interactions.</p