Search results for "Computation"

Corrigendum to “Clinical and genetic update of corneal dystrophies” [YEXER 186C (2019) 107715]

2020

Searching for repetitions in biological networks: methods, resources and tools

2013

We present here a compact overview of the data, models and methods proposed for the analysis of biological networks based on the search for significant repetitions. In particular, we concentrate on three problems widely studied in the literature: ‘network alignment’, ‘network querying’ and ‘network motif extraction’. We provide (i) details of the experimental techniques used to obtain the main types of interaction data, (ii) descriptions of the models and approaches introduced to solve such problems and (iii) pointers to both the available databases and software tools. The intent is to lay out a useful roadmap for identifying suitable strategies to analyse cellular data, possibly based on t…

Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.

2014

There is epidemiological evidence that patients with certain Central Nervous System (CNS) disorders have a lower than expected probability of developing some types of Cancer. We tested here the hypothesis that this inverse comorbidity is driven by molecular processes common to CNS disorders and Cancers, and that are deregulated in opposite directions. We conducted transcriptomic meta-analyses of three CNS disorders (Alzheimer's disease, Parkinson's disease and Schizophrenia) and three Cancer types (Lung, Prostate, Colorectal) previously described with inverse comorbidities. A significant overlap was observed between the genes upregulated in CNS disorders and downregulated in Cancers, as wel…

In silico prediction of central nervous system activity of compounds. Identification of potential pharmacophores by the TOPS–MODE approach

2004

The central nervous system (CNS) activity has been investigated by using a topological substructural molecular approach (TOPS-MODE). A discriminant analysis to classify CNS and non-CNS drugs was developed on a data set (302 compounds) of great structural variability where more than 81% (247/302) were well classified. Randic's orthogonalization procedures was carried out to allow the interpretation of the model and to avoid the collinearity among descriptors. The discriminant model was assessed by a leave-n-out (when n varies from 2 to 20) cross-validation procedure (79.94% of correct classification), an external prediction set composed by 78 CNS/non-CNS drugs (80.77% of correct classificati…

Further monotonicity and convexity properties of the zeros of cylinder functions

1992

AbstractLet cvk be the kth positive zero of the cylinder function Cv(x,α)=Jv(x) cos α−Yv sin α, 0⩽α<π, where Jv(x) and Yv(x) are the Bessel functions of the first and the second kind, respectively. We prove that the function v(d2cvkddv2+δ)cvk increases with v⩾0 for suitable values of δ and k−απ⩾ 0.7070… . From this result under the same conditions we deduce, among other things, that cvk+12δv2 is convex as a function of v⩾0. Moreover, we show some monotonicity properties of the function c2vkv. Our results improve known results.

Application of molecular topology in the prediction of new compounds with anti-trypanosomal cytotoxic activity

2021

La enfermedad de Chagas es una antropozoonosis parasitaria de transmisión mayoritariamente vectorial. Si bien afecta principalmente a América, constituye una de las mayores enfermedades desatendidas a nivel mundial. Solamente dos fármacos con un alto grado de toxicidad se encuentran disponibles para su tratamiento, por lo que es preciso aunar esfuerzos en pos del desarrollo de nuevas drogas antitripanosomales eficaces y con escasos efectos adversos. En este estudio, se aplicó la topología molecular para el desarrollo de un modelo QSAR capaz de predecir la actividad citotóxica antitripanosomal de un grupo de 39 compuestos. El modelo desarrollado mediante análisis lineal discriminante permiti…

Enzymatic effects on reactant and transition states. The case of chalcone isomerase.

2007

Chalcone isomerase catalyzes the transformation of chalcone to naringerin as a part of flavonoid biosynthetic pathways. The global reaction takes place through a conformational change of the substrate followed by chemical reaction, being thus an excellent example to analyze current theories about enzyme catalysis. We here present a detailed theoretical study of the enzymatic action on the conformational pre-equilibria and on the chemical steps for two different substrates of this enzyme. Free-energy profiles are obtained in terms of potentials of mean force using hybrid quantum mechanics/molecular mechanics potentials. The role of the enzyme becomes clear when compared to the counterpart eq…

A Novel Strategy to Study Electrostatic Effects in Chemical Reactions: Differences between the Role of Solvent and the Active Site of Chalcone Isomer…

2015

The electrostatic behavior of active site residues in enzyme catalysis is quite different from that of water molecules in solution. To highlight the electrostatic differences between both environments, we propose a QM/MM strategy to study the role of the environment in chemical reactions. The novelty of the present communication is that free energy surfaces are generated by means of two distinguished reaction coordinates: a solute coordinate and the electrostatic potential created by the environment. This is applied to analyze the origin of catalysis in the transformation of a chalcone into a flavanone, a Michael addition that requires the desolvation of the nucleophile.

E-2-Benzylidenebenzocycloalkanones. IV. Studies on transmission of substituent effects on 13C NMR chemical shifts of E-2-(X-benzylidene)-1-tetralones…

2005

Abstract Single substituent parameter (SSP) and dual substituent parameter (DSP) analyses were applied to study the transmission of substituent effects on selected 13C NMR chemical shifts of the cyclic chalcone analogues, E-2-(4′-X-benzylidene)-1-tetralones (2) and E-2-(4′-X-benzylidene)-1-benzosuberones (3). In order to study how the geometry of the cyclic chalcone analogues affects the transmission of substituent effects similar investigations with the respective chalcones (4) were also performed. The results obtained earlier with the five-membered analogue E-2-(4′-X-benzylidene)-1-indanones (1) were also involved in the comparisons. Geometry optimization of the unsubstituted 1a, 2a, 3a a…

Nonlocal (Pair Site) Reactivity from Second-Order Static Density Response Function:  Gas- and Solution-Phase Reactivity of the Acetaldehyde Enolate a…

1999

A nonlocal (pair site) reactivity scheme is developed and tested. The theory is cast in terms of the first-order Fukui response function f(r,r‘), previously proposed by Fuentealba and Parr [J. Chem. Phys. 1991, 94, 5559]. A change of variables is introduced by using the softness s(r) and t(r) = [∂s(r)/∂N]υ(r) (the variation of softness with respect to the changes in the total number of electrons N at constant external potential υ(r)) that leads to a simple expression for the variation of the Fukui function at site k, namely = − for an electrophilic attack. The first term describes a local contribution, proportional to the variation of the electrostatic potential that can be induced, for exa…