Modeling the chemical impact and the optical emissions produced by lightning-induced electromagnetic fields in the upper atmosphere: the case of halos and elves triggered by different lightning discharges

Halos and elves are Transient Luminous Events (TLEs) produced in the lower ionosphere as a consequence of lightning-driven electromagnetic fields. These events can influence the upper-atmospheric chemistry and produce optical emissions. We have developed different two-dimensional self-consistent models that couple electrodynamical equations with a chemical scheme to simulate halos and elves produced by vertical cloud-to-ground (CG) lightning discharges, Compact Intra-cloud Discharges (CIDs) and Energetic In-cloud Pulses (EIPs). The optical emissions from radiative relaxation of excited states of molecular and atomic nitrogen and oxygen have been calculated. We have upgraded previous local models of halos and elves to calculate for the first time the vibrationally detailed optical spectra of elves triggered by CIDs and EIPs. According to our results, the optical spectra of elves do not depend on the type of parent lightning discharge. Finally, we have quantified the local chemical impact in the upper atmosphere of single halos and elves. In the case of the halo, we follow the cascade of chemical reactions triggered by the lightning-produced electric field during a long-time simulation of up to one second. We obtain a production rate of NO molecules by single halos and elves of 10$^{16}$ and 10$^{14}$ molecules/J, respectively. The results of these local models have been used to estimate the global production of NO by halos and elves in the upper atmopshere at $\sim10^{-7}$ Tg~N/y. This global chemical impact of halos and elves is seven orders of magnitude below the production of NO in the troposphere by lightning discharges

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued e orts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature

Lipophilicity in drug design: an overview of lipophilicity descriptors in 3D-QSAR studies

The pharmacophore concept is a fundamental cornerstone in drug discovery, playing a critical role in determining the success of in silico techniques, such as virtual screening and 3D-QSAR studies. The reliability of these approaches is influenced by the quality of the physicochemical descriptors used to characterize the chemical entities. In this context, a pivotal role is exerted by lipophilicity, which is a major contribution to host-guest interaction and ligand binding affinity. Several approaches have been undertaken to account for the descriptive and predictive capabilities of lipophilicity in 3D-QSAR modeling. Recent efforts encode the use of quantum mechanical-based descriptors derived from continuum solvation models, which open novel avenues for gaining insight into structure-activity relationships studies

On the electrostatic field created at ground level by a halo

We investigate the effect of halo activity on the electrostatic field measured at ground level. We use electrostatic arguments as well as self-consistent simulations to show that, due to the screening charge in the ionosphere, the distant electrostatic field created by the uncompensated charge in a thundercloud decays exponentially rather than as the third power of the distance. Furthermore, significative ionization around the lower edge of the ionosphere slightly reduces the electrostatic field at ground level. We conclude that halos do not extend the range of detectability of lightning-induced electrostatic fields.This work was supported by the Spanish Ministry of Science and Innovation, MINECO under projects ESP2013-48032-C5-5-R, FIS2014-61774-EXP, and ESP2015-69909-C5-2-R and by the EU through the FEDER program. F.J.P.I. acknowledges a MINECO predoctoral contract, code BES-2014-069567. A.L. acknowledges support by a Ramon y Cajal contract, code RYC-2011-07801Peer reviewe

Searching for selective scaffolds against Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase

Malaria is a parasitic disease caused by Plasmodium spp., being one of the major causes of death worldwide with two-hundred million new infections and hundreds of thousands of deaths in 2015. Despite the important advances in its prevention and treatment, its resistance to current drug therapies is still a serious risk in its eradication. There is urgency in finding novel targets and drugs operating by novel mechanisms, avoiding cross-resistance to classical antimalarials. In this context, the bifunctional enzyme Glucose-6- phosphate dehydrogenase 6-phosphogluconolactonase appears to be a promising therapeutic target due to its crucial role in regulating the PPP pathway (pentose phosphate pathway), which is the major source of redox potential in Plasmodium falciparum. In the last few years, our group detected a specific mutation between the human and the Plasmodium falciparum form in the binding site of Glucose-6-phosphate (G6P), the endogenous ligand of Glucose-6-phosphate dehydrogenase (G6PD). This mutation involves the substitution of an Arginine (human) by an Aspartate (parasite), which allowed us to create a validated in-house homology model of PfG6PD. Based on this result, the group has focused their efforts, through different molecular modelling techniques, in the discovery of selective scaffolds against PfG6PD. Current efforts address the development of a complete structural model of the bifunctional enzyme, which may offer novel opportunities to develop molecules capable of inhibiting this relevant enzyme

Global Frequency and Geographical Distribution of Nighttime Streamer Corona Discharges (BLUEs) in Thunderclouds

Blue LUminous Events (BLUEs) are transient corona discharges occurring in thunderclouds and characterized by strong 337.0 nm light flashes with absent (or weak) 777.4 nm component. We present the first nighttime climatology of BLUEs as detected by the Modular Multispectral Imaging Array of the Atmosphere-Space Interaction Monitor showing their worldwide geographical and seasonal distribution. A total (land and ocean) of E~11 BLUEs occur around the globe every second at local midnight and the average BLUE land/sea ratio is E~7:4. The northwest region of Colombia shows an annual nighttime peak. Globally, BLUEs are maximized during the boreal summer-autumn, contrary to lightning which is maximed in the boreal summer. The geographical distribution of nighttime BLUEs shows three main regions in, by order of importance, the Americas, Europe/Africa and Asia/AustraliapublishedVersio