Study of the Differential Activity of Thrombin Inhibitors Using Docking, QSAR, Molecular Dynamics, and MM-GBSA

Indexación: Web of Science; Scopus.Non-peptidic thrombin inhibitors (TIs; 177 compounds) with diverse groups at motifs P1 (such as oxyguanidine, amidinohydrazone, amidine, amidinopiperidine), P2 (such as cyano-fluorophenylacetamide, 2-(2-chloro-6-fluorophenyl)acetamide), and P3 (such as phenylethyl, arylsulfonate groups) were studied using molecular modeling to analyze their interactions with S1, S2, and S3 subsites of the thrombin binding site. Firstly, a protocol combining docking and three dimensional quantitative structure-activity relationship was performed. We described the orientations and preferred active conformations of the studied inhibitors, and derived a predictive CoMSIA model including steric, donor hydrogen bond, and acceptor hydrogen bond fields. Secondly, the dynamic behaviors of some selected TIs (compounds 26, 133, 147, 149, 162, and 177 in this manuscript) that contain different molecular features and different activities were analyzed by creating the solvated models and using molecular dynamics (MD) simulations.We used the conformational structures derived from MD to accomplish binding free energetic calculations using MM-GBSA. With this analysis, we theorized about the effect of van der Waals contacts, electrostatic interactions and solvation in the potency of TIs. In general, the contents reported in this article help to understand the physical and chemical characteristics of thrombin-inhibitor complexes. © 2015 Mena-Ulecia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.014277

Theoretical design of stable small aluminium-magnesium binary clusters

We explore in detail the potential energy surfaces of the AlxMgy (x, y = 1–4) systems as case studies to test the utility and limitations of simple rules based on electron counts and the phenomenological shell model (PSM) for bimetallic clusters. We find that it is feasible to design stable structures that are members of this set of small Al–Mg binary clusters, using simple electron count rules, including the classical 4n + 2 Hückel model, and the most recently proposed PSM. The thermodynamic stability of the title compounds has been evaluated using several different descriptors, including the fragmentation energies and the electronic structure of the systems. Three stable systems emerge from the analysis: the Al4Mg, Al2Mg2 and Al4Mg4 clusters. The relative stability of Al4Mg is explained by the stability of the Al42− subunit to which the Mg atom donates its electrons. Here the Mg2+ sits above the aromatic 10 π-electron Al42− planar ring. The Al2Mg2 and Al4Mg4 clusters present more complicated 3D structures, and their stabilities are rationalized as a consequence of their closed shell nature in the PSM, with 10 and 20 itinerant electrons, respectively

Planar Hexacoordinate Carbons: Half Covalent, Half Ionic

Indexación ScopusHerein, the first global minima containing a planar hexacoordinate carbon (phC) atom are reported. The fifteen structures belong to the CE3M3+ (E=S–Te and M=Li–Cs) series and satisfy both geometric and electronic criteria to be considered as a true phC. The design strategy consisted of replacing oxygen in the D3h CO3Li3+ structure with heavy and less electronegative chalcogens, inducing a negative charge on the C atom and an attractive electrostatic interaction between C and the alkali-metal cations. The chemical bonding analyses indicate that carbon is covalently bonded to three chalcogens and ionically connected to the three alkali metals. © 2021 Wiley-VCH GmbHhttps://onlinelibrary-wiley-com.recursosbiblioteca.unab.cl/doi/10.1002/anie.20210094

Pollen-Mediated Gene Flow in Maize: Implications for Isolation Requirements and Coexistence in Mexico, the Center of Origin of Maize

Mexico, the center of origin of maize (Zea mays L.), has taken actions to preserve the identity and diversity of maize landraces and wild relatives. Historically, spatial isolation has been used in seed production to maintain seed purity. Spatial isolation can also be a key component for a strategy to minimize pollen-mediated gene flow in Mexico between transgenic maize and sexually compatible plants of maize conventional hybrids, landraces, and wild relatives. The objective of this research was to generate field maize-to-maize outcrossing data to help guide coexistence discussions in Mexico. In this study, outcrossing rates were determined and modeled from eight locations in six northern states, which represent the most economically important areas for the cultivation of hybrid maize in Mexico. At each site, pollen source plots were planted with a yellow-kernel maize hybrid and surrounded by plots with a white-kernel conventional maize hybrid (pollen recipient) of the same maturity. Outcrossing rates were then quantified by assessing the number of yellow kernels harvested from white-kernel hybrid plots. The highest outcrossing values were observed near the pollen source (12.9% at 1 m distance). The outcrossing levels declined sharply to 4.6, 2.7, 1.4, 1.0, 0.9, 0.5, and 0.5% as the distance from the pollen source increased to 2, 4, 8, 12, 16, 20, and 25 m, respectively. At distances beyond 20 m outcrossing values at all locations were below 1%. These trends are consistent with studies conducted in other world regions. The results suggest that coexistence measures that have been implemented in other geographies, such as spatial isolation, would be successful in Mexico to minimize transgenic maize pollen flow to conventional maize hybrids, landraces and wild relatives

Fabrication of macro-mesoporous zirconia-alumina materials with a one-dimensional hierarchical structure

A series of one dimensional (1D) zirconia/alumina nanocomposites were prepared by the deposition of zirconium species onto the 3D framework of boehmite nanofibres formed by dispersing boehmite nanofibres into butanol solution. The materials were calcined at 773K and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscope (TEM), N2 adsorption/desorption, infrared emission spectroscopy (IES). The results demonstrated that when the molar percentage X=100*Zr/(Al+Zr) was > 30 %, extremely long ZrO2/Al2O3 composite nanorods with evenly distributed ZrO2 nanocrystals on the surface were formed. The stacking of such nanorods gave rise to a new kind of macroporous material without the use of any organic space filler\template or other specific technologies. The mechanism for the formation of long ZrO2/Al2O3 composite nanorods was proposed in this work

Exploring the potential energy surface of small lead clusters using the gradient embedded genetic algorithm and an adequate treatment of relativistic effects

Indexación: Scopus.It is a well-known fact that theoretical methodologies play a crucial role to assure an adequate structural assignment of gas-phase clusters. Particularly, in heavy-element containing clusters the inclusion of relativistic effects (scalar and spin-orbit coupling) can significantly affect their chemistry. Therefore, these effects become the keystone on their structural determination. In our work, the way in which relativistic effects were treated, as well as their influence in the process of an adequate identification of lowest-energy isomer (the global minima-"GM"-energy structure), were evaluated in small lead clusters. The potential energy surfaces of small Pbn (n = 3-10) clusters was explored by means of the gradient embedded genetic algorithm program (GEGA). Subsequently, the most stable isomers were re-optimized incorporating relativistic effects through two different approximations: (i) using relativistic effective core potentials (RECPs) or pseudopotentials, which mimics the scalar and spin-orbit coupling relativistic effects (SR and SO) of the core electrons; and (ii) using relativistic Hamiltonians (with proper all-electron basis sets), like, the zeroth-order regular approximation (ZORA) to the Dirac equation, in which the scalar (SR) and spin-orbit coupling (SOC) relativistic effects were also included. The results evidence that methodologies including SOC effect allow to identify the GM energy structure correctly in all the studied cases. Besides, the GEGA algorithm, using a modest RECP, provides good initial structures that become GM after re-optimization at the SOC level.http://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C7RA11449D#!divAbstrac