Prediction of binding energies upon mutation in 3D-structure-known complexes through PyDock scoring functions

The main objective of this work is to build a simple but robust predictor of binding energy changes upon mutation, once structural information is provided. Three different tools are being employed: First, given the wild type structure of a complex, mutations are modelled with Modeller, a powerful program extensively used in protein homology modeling. Using the workframe provided by the tool, 50 different models are created for each mutation. This model diversity helps to take into account protein flexibility and explore, more efficiently, the conformational space of interactions.Then, models are evaluated using Modeller DOPE assessment tool and pyDock scoring function. DOPE [7] is statistical-potential-based tool that evaluates the quality of a model. The pyDock scoring function [8] is formed by different energy terms (electrostatic, desolvation and van der Waals), and was originally designed to deal with protein-protein docking problems. However, due to its energetic basis, we wanted to test their ability to evaluate changes in binding energies

The rocaille victory: the chapel altarpiece of the Sagrada Familia school in Seville, Francisco de Acosta el Mayor’s work

Vinculamos el retablo de la capilla del colegio Sagrada Familia de Sevilla a Francisco de Acosta “el Mayor”, el cual procede del conjunto que hizo para el Carmen Calzado de Carmona entre 1770 y 1772 y que actualmente se encuentra disperso.We link the altarpiece at Sagrada Familia School’s chapel in Seville to Francisco de Acosta “el Mayor”, which proceeds from the set that he built for the Carmen Calzado Convent in Carmona between 1770 and 1772 and that is dispersed nowadays

Response: Commentary: Past, present and future of epigenetics applied to livestock breeding

Following our recent Review article (González-Recio et al., 2015), we received correspondence by Steele (2016). We thank Dr. Steele for his comments, which provide a thorough review of his work on human immunology, which has persuaded him that “hard types of soma-to-germline transfer are ongoing at very high frequency in human immune system germlines.” His and other researchers' studies on reverse transcriptase (RT) based feedback mechanisms showed that RNA could be retrotranscripted to DNA, and it can be inserted into the mammalian germline, and therefore be transferred to the progeny

Le modèle espagnol de direction

Comment la réforme globale du système éducatif espagnol, votée en 1990, affecte-t-elle le mode de direction des établissements ? Les spécificités de ce fonctionnement (équipe de direction élue, implication de la communauté éducative) sont analysées dans le cadre de la nouvelle autonomie, pédagogique et financière, accordée aux établissements

Deeply bound levels in kaonic atoms

Using a microscopic antikaon-nucleus optical potential recently developed by Ramos and Oset [10] from a chiral model, we calculate strong interaction energy shifts and widths for K- atoms. This purely theoretical potential gives an acceptable description of the measured data (chi(2)/num.data = 3.8), though it turns out to be less attractive than what can be inferred from the existing kaon atomic data. We also use a modified potential, obtained by adding to the latter theoretical one a s-wave term which is fitted to known experimental kaonic data (chi(2)/degree of freedom = 1.6), to predict deeply bound K- atomic levels, not yet detected. This improved potential predicts, in general, states even narrower than those recently reported by Friedman and Gal [9]. This reinforces the idea that these deeply atomic states can be detected and resolved by using suitable nuclear reactions. Besides, we also study K- and (K) over bar(0) nuclear bound states and compute binding energies and widths, for both species of antikaons, in C-12, Ca-40 and Pb-208. Despite of restricting our study only to potentials obtained from best fits to the known kaonic atom data, the dynamics of these nuclear bound states depends dramatically on the particular optical potential used

LightDock: a new multi-scale approach to protein–protein docking

Computational prediction of protein–protein complex structure by docking can provide structural and mechanistic insights for protein interactions of biomedical interest. However, current methods struggle with difficult cases, such as those involving flexible proteins, low-affinity complexes or transient interactions. A major challenge is how to efficiently sample the structural and energetic landscape of the association at different resolution levels, given that each scoring function is often highly coupled to a specific type of search method. Thus, new methodologies capable of accommodating multi-scale conformational flexibility and scoring are strongly needed. We describe here a new multi-scale protein–protein docking methodology, LightDock, capable of accommodating conformational flexibility and a variety of scoring functions at different resolution levels. Implicit use of normal modes during the search and atomic/coarse-grained combined scoring functions yielded improved predictive results with respect to state-of-the-art rigid-body docking, especially in flexible cases.B.J-G was supported by a FPI fellowship from the Spanish Ministry of Economy and Competitiveness. This work was supported by I+D+I Research Project grants BIO2013-48213-R and BIO2016-79930-R from the Spanish Ministry of Economy and Competitiveness. This work is partially supported by the European Union H2020 program through HiPEAC (GA 687698), by the Spanish Government through Programa Severo Ochoa (SEV-2015-0493), by the Spanish Ministry of Science and Technology (TIN2015-65316-P) and the Departament d’Innovació, Universitats i Empresa de la Generalitat de Catalunya, under project MPEXPAR: Models de Programaciói Entorns d’Execució Paral·lels (2014-SGR-1051).Peer ReviewedPostprint (author's final draft

Past, present and future of epigenetics applied to livestock breeding

This article reviews the concept of Lamarckian inheritance and the use of the term epigenetics in the field of animal genetics. Epigenetics was first coined by Conrad Hal Waddington (1905–1975), who derived the term from the Aristotelian word epigenesis. There exists some controversy around the word epigenetics and its broad definition. It includes any modification of the expression of genes due to factors other than mutation in the DNA sequence. This involves DNA methylation, post-translational modification of histones, but also linked to regulation of gene expression by non-coding RNAs, genome instabilities or any other force that could modify a phenotype. There is little evidence of the existence of transgenerational epigenetic inheritance in mammals, which may commonly be confounded with environmental forces acting simultaneously on an individual, her developing fetus and the germ cell lines of the latter, although it could have an important role in the cellular energetic status of cells. Finally, we review some of the scarce literature on the use of epigenetics in animal breeding programs

Structural and energy determinants in protein-RNA docking

Deciphering the structural and energetic determinants of protein-RNA interactions harbors the potential to understand key cell processes at molecular level, such as gene expression and regulation. With this purpose, computational methods like docking aim to complement current biophysical and structural biology efforts. However, the few reported docking algorithms for protein-RNA interactions show limited predictive success rates, mainly due to incomplete sampling of the conformational space of both the protein and the RNA molecules, as well as to the difficulties of the scoring function in identifying the correct docking models. Here, we have tested the predictive value of a variety of knowledge-based and energetic scoring functions on a recently published protein-RNA docking benchmark and developed a scoring function able to efficiently discriminate docking decoys. We first performed docking calculations with the bound conformation, which allowed us to analyze the problem in optimal conditions. We found that geometry-based terms and electrostatics were the most important scoring terms, while binding propensities and desolvation were much less relevant for the scoring of protein-RNA models. This is in contrast with what we observed for protein-protein docking. The results also showed an interesting dependence of the predictive rates on the flexibility of the protein molecule, which arises from the observed higher positive charge of flexible interfaces and provides hints for future development of more efficient protein-RNA docking methods.This work is supported by grant BIO2013-48213-R from Plan Nacional I+D+i (Spanish Ministry of Economy and Competitiveness). LP-C was recipient of an FPU fellowship from the Spanish Ministry of Science.Peer ReviewedPostprint (author's final draft

The class of all 3-valued natural conditional variants of RM3 that are Plumwood Algebras

Valerie Plumwood introduced in "Some false laws of logic" a series of arguments on how the rules Exported Syllogism, Disjunctive Syllogism, Commutation, and Exportation are not acceptable. Based on this we define the class of Plumwood algebras - logical matrices that do not verify any of these theses. Afterwards we provide conditional variants of the characteristic matrix of the logic RM3 that are also Plumwood algebras. These matrices are given an axiomatization based on First Degree Entailment and are endowed with Belnap-Dunn Semantics. Finally we provide results of Soundness and Completeness in the strong sense for each of the defined variants