The Construction of the Tower of Pisa as a Basis for Problem-Solving in the Exact Sciences and the Use of Interdisciplinarity in Teaching

Background: Learning in exact sciences is a common problem for education in all countries. New education technologies are proposed to solve these situations, and using real problems in teaching is suggested. Objectives: This article associates Pólya’s problem-solving method with the real problems in the construction of the Tower of Pisa. Design: In this work, we propose a multidisciplinary approach to the history of the construction of the Tower of Pisa, related to the social, historical, geological, and mainly physics and engineering problems shown in this work. Setting and participants: The authors were responsible for elaborating and solving the proposed problems.   Data collection and analysis: The data used come from the history of the Leaning Tower of Pisa as a pedagogical basis for teaching, especially in the exact sciences. Results: Many problems and resolutions via Pólya’s problem-solving method were performed to show teaching possibilities to teachers and students. Conclusions: The Tower of Pisa theme can be used to implement new education technologies, such as modelling, problem-solving, and real-life problems, as it enriches school culture and attracts an inter-and multidisciplinary character to teaching, as shown through the proposed teaching in exact sciences examples

Molecular Docking in Drug Discovery: Techniques, Applications, and Advancements

Objective: The primary objective of this study is to conduct a comprehensive review of the significance of molecular docking in the field of drug discovery. This includes an examination of the various approaches and methods used in molecular docking, as well as an exploration of the techniques used for interpreting and validating docking results. Methods: To gather relevant data, a systematic search was conducted using Web of Science, PubMed, and Google Scholar. The search focused on articles related to molecular docking methodologies and their applications in drug discovery. Additionally, alternative techniques that can be used for more precise simulations of ligand-protein interactions were also considered. Results: Molecular docking has proven to be an incredibly rich and valuable process in the field of drug discovery. Its flexibility allows for the incorporation of advanced computational techniques, thereby enhancing the reliability and efficiency of drug discovery processes. The results of the study highlight the significant strides made in the field of molecular docking, demonstrating its potential to revolutionize drug discovery. Conclusions: Molecular docking continues to evolve, with new advancements being made regularly. Despite the challenges faced, these advancements have significantly contributed to the enhancement of molecular docking, solidifying its position as a crucial tool in the field of drug discovery

Exploring the System Lanthanide/Succinate in the Formation of Porous Metal–Organic Frameworks: Experimental and Theoretical Study

Exploring the Ln/succinate system and the template effect in hydrothermal synthesis made it possible to obtain [La₂(Succ)₃(H₂O)₃]·2H₂O and [Ln₂(Succ)₃(H₂O)₂] where Ln = La, Pr, Nd, Sm, Eu, Gd, and Tb. The first case is a 2D network with a sql plane net topology. The 3D supramolecular network is formed by strong hydrogen bonds, which give rise to a pcu network. In the second case, a family of 3D compounds with a bnn topology could be synthesized. Both compounds can be obtained in the presence of 5-sulfosalicylate (5-SSA^3–) as a template agent, and the presence of toluene in the reaction enables formation only of [Ln₂(Succ)₃(H₂O)₂] compounds. This paper addresses a systematic synthetic and theoretical study of the formation equilibrium of the molecules reported. The influence of the template agent on the formation of porous MOFs and the luminescent behavior are addressed

Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies

All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (Mpro) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively

Genomic landscape of the emerging XDR Salmonella Typhi for mining druggable targets clpP, hisH, folP and gpmI and screening of novel TCM inhibitors, molecular docking and simulation analyses

Abstract Typhoid fever is transmitted by ingestion of polluted water, contaminated food, and stool of typhoid-infected individuals, mostly in developing countries with poor hygienic environments. To find novel therapeutic targets and inhibitors, We employed a subtractive genomics strategy towards Salmonella Typhi and the complete genomes of eight strains were primarily subjected to the EDGAR tool to predict the core genome (n = 3207). Human non-homology (n = 2450) was followed by essential genes identification (n = 37). The STRING database predicted maximum protein-protein interactions, followed by cellular localization. The virulent/immunogenic ability of predicted genes were checked to differentiate drug and vaccine targets. Furthermore, the 3D models of the identified putative proteins encoded by the respective genes were constructed and subjected to druggability analyses where only “highly druggable” proteins were selected for molecular docking and simulation analyses. The putative targets ATP-dependent CLP protease proteolytic subunit, Imidazole glycerol phosphate synthase hisH, 7,8-dihydropteroate synthase folP and 2,3-bisphosphoglycerate-independent phosphoglycerate mutase gpmI were screened against a drug-like library (n = 12,000) and top hits were selected based on H-bonds, RMSD and energy scores. Finally, the ADMET properties for novel inhibitors ZINC19340748, ZINC09319798, ZINC00494142, ZINC32918650 were optimized followed by binding free energy (MM/PBSA) calculation for ligand-receptor complexes. The findings of this work are expected to aid in expediting the identification of novel protein targets and inhibitors in combating typhoid Salmonellosis, in addition to the already existing therapies

Camu-camu (Myrciaria dubia) seeds as a novel source of bioactive compounds with promising antimalarial and antischistosomicidal properties

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In Silico Studies of the Biomolecular Interactions Between Natural Products and SARS-CoV-2 Main Protease

The rapid global spread of SARS-CoV-2, the causative agent of COVID-19, has set off the alarms of healthcare systems all over the world, the situation is exacerbated as no effective treatment is available to date. One therapeutic strategy consists in stopping the replication of the virus by inhibiting SARS-CoV-2 main protease, an important enzyme in the processing of polyproteins from viral RNA. Applying techniques like virtual screening, molecular docking and molecular dynamics simulations, our study evaluated the biomolecular interactions generated between more than 200 thousand natural products structures collected from the Universal Natural Product Database and the main protease active site. Through successive docking filters, we identified 3 molecules with a good affinity profile for the enzyme. These were subjected to molecular dynamics simulations and their binding free energies were calculated. Structures of the best natural products identified could be a starting point for developing novel antiviral candidates targeting SARS-CoV-2 Mpro</sup

Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2

The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its spread since 2019 represents the major public health problem worldwide nowadays, generating a high number of infections and deaths. That’s why, in addition to vaccination campaigns, the design of a drug to help in the treatment of severe cases of COVID-19 is being investigated. In relation to SARS-CoV-2, one of its most studied proteins is the spike protein (S protein), which mediates host-cell entry and is heavily glycosylated. Regarding the latter, several investigations have been carried out, since it plays an important role in the evasion of the host\u27s immune system and contributes to protein folding and the thermostability of the viral particle. For that reason, our objective was to evaluate the impact of glycosylations on the drug recognition on two domains of the S protein, the receptor-binding domain (RBD) and the N-terminal domain (NTD) through molecular dynamics simulations and computational biophysics analysis. Our results show that glycosylations in the S protein induce structural stability and changes in rigidity/flexibility related to the number of glycosylations in the structure. These structural changes are important for its biological activity as well as the correct interaction of ligands in the RBD and NTD regions. Additionally, we evidenced a roto-translation phenomenon in the interaction of the ligand with RBD in the absence of glycosylation, which disappears due to the influence of glycosylation and the convergence of metastable states in RBM. Similarly, glycosylations in NTD promote an induced-fit phenomenon, which is not observed in the absence of glycosylations; this process is decisive for the activity of the ligand at the cryptic site. Altogether, these results provide an explanation of glycosylation relevance in biophysical properties and drug recognition to S protein of SARS-CoV-2 which must be considered in the rational drug development and virtual screening targeting S protein