Modeling DNA Oligonucleotide Binding to DNA-mimetic Stem-Loop 1 of the SARS-CoV-2 RNA

SARS-CoV-2 is a positive-sense RNA virus that contains open reading frame 1ab (ORF1ab) to produce 16 nonstructural proteins (nsps). Five stem-loops (SL) are found in the 5' UTR of the RNA that are involved in myriad viral functions and are labeled SL1 through SL5. SL1 is crucial to viral replication. Upon viral infection, nsp1 binds the ribosomal 40S subunit to inhibit all host mRNA translation. Upon SL1 binding to nsp1, viral mRNA can be processed by the ribosome, allowing viral proteins to be produced. In this study, we are examining small DNA oligonucleotides that bind to SL1-mimetic DNA in order to block SL1-nsp1 interactions. We designed a DNA analog of the SL1 hairpin and two small DNA oligonucleotides that are complementary to either the helical stem or the loop region of SL1. The binding of these oligonucleotides to the SL1 hairpin should allow the formation of either an alternate duplex or a triplex structure. Isothermal titration calorimetry (ITC) and circular dichroism (CD) techniques were performed in 1 MKCl and 10 mM MgCl2 at two different pH (5.5 and 7.0) to examine structural and thermodynamics of binding. ITC of the two oligonucleotides showed modest binding. Results from DNA binding experiments, thermal denaturation, and CD show the hairpin structure is thermodynamically more favored and mostly remains intact under the conditions examined.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

An optimized thermodynamics integration protocol for identifying beneficial mutations in antibody design.

Accurate identification of beneficial mutations is central to antibody design. Many knowledge-based (KB) computational approaches have been developed to predict beneficial mutations, but their accuracy leaves room for improvement. Thermodynamic integration (TI) is an alchemical free energy algorithm that offers an alternative technique for identifying beneficial mutations, but its performance has not been evaluated. In this study, we developed an efficient TI protocol with high accuracy for predicting binding free energy changes of antibody mutations. The improved TI method outperforms KB methods at identifying both beneficial and deleterious mutations. We observed that KB methods have higher accuracies in predicting deleterious mutations than beneficial mutations. A pipeline using KB methods to efficiently exclude deleterious mutations and TI to accurately identify beneficial mutations was developed for high-throughput mutation scanning. The pipeline was applied to optimize the binding affinity of a broadly sarbecovirus neutralizing antibody 10-40 against the circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant. Three identified beneficial mutations show strong synergy and improve both binding affinity and neutralization potency of antibody 10-40. Molecular dynamics simulation revealed that the three mutations improve the binding affinity of antibody 10-40 through the stabilization of an altered binding mode with increased polar and hydrophobic interactions. Above all, this study presents an accurate and efficient TI-based approach for optimizing antibodies and other biomolecules.

Contribution of the catalytic dyad of SARS-CoV-2 main protease to binding covalent and noncovalent inhibitors.

The effect of mutations of the catalytic dyad residues of SARS-CoV-2 main protease (MProWT) on the thermodynamics of binding of covalent inhibitors comprising nitrile [nirmatrelvir (NMV), NBH2], aldehyde (GC373), and ketone (BBH1) warheads to MPro is examined together with room temperature X-ray crystallography. When lacking the nucleophilic C145, NMV binding is ∼400-fold weaker corresponding to 3.5 kcal/mol and 13.3 °C decrease in free energy (ΔG) and thermal stability (Tm), respectively, relative to MProWT. The H41A mutation results in a 20-fold increase in the dissociation constant (Kd), and 1.7 kcal/mol and 1.4 °C decreases in ΔG and Tm, respectively. Increasing the pH from 7.2 to 8.2 enhances NMV binding to MProH41A, whereas no significant change is observed in binding to MProWT. Structures of the four inhibitor complexes with MPro1-304/C145A show that the active site geometries of the complexes are nearly identical to that of MProWT with the nucleophilic sulfur of C145 positioned to react with the nitrile or the carbonyl carbon. These results support a two-step mechanism for the formation of the covalent complex involving an initial non-covalent binding followed by a nucleophilic attack by the thiolate anion of C145 on the warhead carbon. Noncovalent inhibitor ensitrelvir (ESV) exhibits a binding affinity to MProWT that is similar to NMV but differs in its thermodynamic signature from NMV. The binding of ESV to MProC145A also results in a significant, but smaller, increase in Kd and decrease in ΔG and Tm, relative to NMV.

Two years of COVID-19. Impacts on accessibility of a mental health service for immigrants and individuals in socio-economic difficulties

We extend our previous investigation of the effects of prehydrodynamic evolution on final-state observables in heavy-ion collisions [38] to smaller systems. We use a state-of-the-art hybrid model for the numerical simulations with optimal parameters obtained from a previous Bayesian study. By studying p-Pb collisions, we find that the effects due to the assumption of a conformal evolution in the prehydrodynamical stage are even more important in small systems. We also show that this effect depends on the time duration of the pre-equilibrium stage, which is further enhanced in small systems. Finally, we show that the recent proposal of a free-streaming with subluminal velocity for the pre-equilibrium stage, thus effectively breaking conformal invariance, can alleviate the contamination of final-state observables. Our study further reinforces the need for moving beyond conformal approaches in pre-equilibrium dynamics modeling, especially when extracting transport coefficients from hybrid models in the high-precision era of heavy-ion collisions.

16th International Conference on the Modelling of Casting, Welding, and Advanced Solidification Processes

PrefaceThe 16th International Conference on the Modelling of Casting, Welding, and Advanced Solidification Processes (MCWASP XVI) was held from June 18 to 23, 2023, in Banff, Canada, at the Banff Centre for Arts and Creativity. Founded in 1933, the Centre in Treaty 7 Territory within Banff National Park—Canada's first National Park—is a learning organization built upon an extraordinary legacy of excellence in artistic and creative development. The "all-inclusive” nature of the conference and the remote setting meant that participants dined, attended oral and poster presentations, and participated in social activities as a group, fostering outstanding opportunities for networking.Given that the MCWASP community had not met in person since 2015 in Japan (the 2020 edition of MCWASP was virtual owing to COVID-19), the 2023 conference provided the opportunity to renew old friendships and make new ones as well as discuss the science of solidification and related processes—all within the backdrop of the beautiful Canadian Rocky Mountains.The technical program comprised more than 70 oral and poster presentations. In addition to content related to modelling of casting, welding, and advanced solidification processes, keynotes were invited to talk about related subjects (artificial intelligence/machine learning, and permeability modelling in shale rock) as well as the rich diversity of fossils, especially dinosaurs, found in Alberta.The oral technical program was organized with as a single session (i.e., no concurrent presentations). It featured all aspects of solidification modelling, including solidification process technologies (continuous and semi-continuous casting, shape casting, additive manufacturing, and welding), coupled multi-physics simulations, defect formation, fluid flow, micro- and macro-structure formation, numerical methods, and related experimentation, especially in-situ observation of solidification.The four-day technical program was spread over five days to give participants the opportunity to explore the stunning Canadian Rocky Mountains.In these proceedings, the papers are organized by major theme. The dominant topics are Additive Manufacturing and Welding and Microstructure Formation, followed by Continuous Casting – Shape Casting, Heat Transfer and Fluid Flow, Alloy Segregation, Defects, Imaging of Solidification, Thermomechanics, and Materials Properties. In these themes, the authors report advances in numerical modelling techniques, new scientific and process developments in solidification, and related in-situ experimentation.Although significant progress has been made over these past 16 MCWASP conferences covering 43 years, it is clear that the complexity of advanced solidification phenomena as related to conventional and emerging manufacturing technologies still attracts a great deal of scientific and industrial interest to support technological innovation.André PhillionBanff, Canada, June 2023MCWASP XVI 2023List of Peer Reviewers, Sponsors, MCWASP XVI Organizers, International Scientific Committee are available in this Pdf.

Structural and Computational Studies of Cobalt(II) and Copper(II) Complexes with Aromatic Heterocyclic Ligand

Two coordination complexes, a cobalt(II) complex tris(1,10-phenanthroline)-cobalt perchlorate hydrate, [Co(phen)3]·(ClO4)2·H2O(1), and a copper(II) complex tris(1,10-phenanthroline)-copper perchlorate 4-bromo-2-{[(naphthalene-1-yl)imino]methyl}phenol hydrate, [Cu(phen)3]·(ClO4)2·HL·[O] (2), [where, phen = 1,10-phenathroline as aromatic heterocyclic ligand, HL = 4-bromo-2-((Z)-(naphthalene-4-ylimino) methyl) phenol] have been synthesized and structurally characterized. Single crystal X-ray analysis of both complexes has revealed the presence of a distorted octahedral geometry around cobalt(II) and copper(II) ions. density functional theory (DFT)-based quantum chemical calculations were performed on the cationic complex [Co(phen)3]2+ and copper(II) complex [Cu(phen)3]2+ to get the structure property relationship. Hirshfeld surface and 2-D fingerprint plots have been explored in the crystal structure of both the metal complexes. To find potential SARS-CoV-2 drug candidates, both the complexes were subjected to molecular docking calculations with SARS-CoV-2 virus (PDB ID: 7BQY and 7C2Q). We have found stable docked structures where docked metal chelates could readily bound to the SARS-CoV-2 Mpro. The molecular docking calculations of the complex (1) into the 7C2Q-main protease of SARS-CoV-2 virus revealed the binding energy of −9.4 kcal/mol with a good inhibition constant of 1.834 µM, while complex (2) exhibited the binding energy of −9.0 kcal/mol, and the inhibition constant of 1.365 µM at the inhibition binding site of receptor protein. Overall, our in silico studies explored the potential role of cobalt(II) complex (1), and copper(II) complex (2) complex as the viable and alternative therapeutic solution for SARS-CoV-2.

Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2.

Mutations drive viral evolution and genome variability that causes viruses to escape host immunity and to develop drug resistance. SARS-CoV-2 has considerably higher mutation rate. SARS-CoV-2 possesses a RNA dependent RNA polymerase (RdRp) which helps to replicate its genome. The mutation P323L in RdRp is associated with the loss of a particular epitope (321-327) from this protein. We consider the effects of mutations in some of the epitope region including the naturally occurring mutation P323L on the structure of the epitope and their interface with paratope using all-atom molecular dynamics (MD) simulation studies. We observe that the mutations cause conformational changes in the epitope region by opening up the region associated with increase in the radius of gyration and intramolecular hydrogen bonds, making the region less accessible. Moreover, we study the conformational stability of the epitope region and epitope:paratope interface under the mutation from the fluctuations in the dihedral angles. We observe that the mutation renders the epitope and the epitope:paratope interface unstable compared to the corresponding wild type ones. Thus, the mutations may help in escaping antibody mediated immunity of the hostCommunicated by Ramaswamy H. Sarma.

In-depth study of kinetics, thermodynamics, and reaction mechanism of catalytic pyrolysis of disposable face mask using spent adsorbent based catalysts

Millions of face mask has been converted to waste since the onset of COVID-19 virus. Hence, present study explores the feasibility of converting disposable face masks to energy through catalytic pyrolysis process using a low-cost waste (spent aluminum hydroxide/oxide nanoparticle adsorbent) derived catalyst. Thermogravimetric analysis of the non-catalytic and catalytic pyrolysis of disposable face mask was conducted at varied heating rates of 10 °C/min, 20 °C/min, 30 °C/min, 40 °C/min, and 50 °C/min, respectively. Iso-conversional methods, Kissinger Akahira Sunose (KAS) and Ozawa Flynn Wall (OFW) were used for the kinetic study. The reaction mechanism was analyzed using Criado's z-master plot (CZMP) method along with the determination of thermodynamic parameters of the process. Results found that the addition of a catalyst to the process benefits the overall efficacy of the process by reducing the activation energy (Ea) (without catalyst;OFW-Ea: 188.7 kJ/mol, KAS-Ea: 186.2 kJ/mol) as well as lowering the disordered state of the process. Metal doped catalyst (Ni/ γ-Al2O3) (OFW-Ea: 168.4 kJ/mol, KAS-Ea: 167.8 kJ/mol) shows a larger reduction in activation energy in comparison to bare alumina (γ-Al2O3) (OFW-Ea: 183.2 kJ/mol, KAS-Ea: 180.4 kJ/mol). The current study presented disposable face masks as reclaimable in terms of energy and waste-derived catalyst as a potent solution to be explored in place of high-cost commercial catalysts. © 2023 Energy Institute

Assimilation of aircraft observations over the Indian monsoon region: Investigation of the effects of COVID-19 on a reanalysis

Since March 2020, the COVID-19 pandemic has significantly reduced the availability of global aircraft-based observations (ABOs), which has been restored later in 2021. This study focuses on the impact of ABOs on a regional reanalysis. Indian Monsoon Data Assimilation and Analysis (IMDAA) is a regional reanalysis for a period from 1979 to 2020 (originally up to 2018) over India and surrounding regions produced at the National Centre for Medium Range Weather Forecasting (NCMRWF), India, in collaboration with the UK Met Office. A comparison of the impact of ABOs on other conventional and satellite observations assimilated in the NCMRWF global model and IMDAA during 2019 and 2020 revealed the importance of ABOs, particularly in IMDAA, since it did not assimilate the latest satellite data as the IMDAA system was frozen in October 2016. A data denial experiment that removes all the ABOs from the IMDAA assimilation system for a period from March to November 2019 is designed. The results from the IMDAA reanalysis run, which assimilates ABOs during the same period, are compared with the data denial experiment. Assimilation of ABOs strengthened the upper tropospheric circulation, the Tropical Easterly Jet (TEJ), during the Indian summer monsoon compared to the data denial experiment. Analysis of the features of two cyclones that developed over the North Indian Ocean during the study period revealed that ABO assimilation played a key role in simulating the track and intensity of these cyclones when they were in the ‘severe' category. Since the sample is small, more cyclone cases need to be analysed to consolidate the result. © 2023 Royal Meteorological Society.

The Potential Impact of Ayurvedic Traditional Bhasma on SARS-CoV-2-Induced Pathogenesis

The mass casualties caused by the delta variant and the wave of the newer "Omicron" variant of SARS-COV-2 in India have brought about great concern among healthcare officials. The government and healthcare agencies are seeking effective strategies to counter the pandemic. The application of nanotechnology and repurposing of drugs are reported as promising approaches in the management of COVID-19 disease. It has also immensely boomed the search for productive, re-liable, cost-effective, and bio-assimilable alternative solutions. Since ancient times, the traditional-ly employed Ayurvedic bhasmas have been used for diverse infectious diseases, which are now employed as nanomedicine that could be applied for managing COVID-19-related health anomalies. Like currently engineered metal nanoparticles (NPs), the bhasma nanoparticles (BNPs) are also packed with unique physicochemical properties, including multi-elemental nanocrystalline compo-sition, size, shape, dissolution, surface charge, hydrophobicity, and multi-pathway regulatory as well as modulatory effects. Because of these conformational and configurational-based physico-chemical advantages, Bhasma NPs may have promising potential to manage the COVID-19 pandemic and reduce the incidence of pneumonia-like common lung infections in children as well as age-related inflammatory diseases via immunomodulatory, anti-inflammatory, antiviral, and adju-vant-related properties.Copyright © 2023 Bentham Science Publishers.

INDUSTRY-BASED THERMODYNAMICS CASE STUDY ON REFRIGERATION CYCLE

The case study learning methodology has been used for more than 20 years in teaching science and engineering. This methodology is known to be highly effective in promoting students' understanding of the concepts and improving their ability to make connections between the concepts. In 2020 and 2021, the limited access to laboratory equipment and facilities due to the COVID-19 pandemic encouraged instructors to implement alternative methods. One of the alternatives considered in the current institution is the use of case studies to enhance students' understanding of thermodynamics and fluid mechanics topics during the online and hybrid implementations of those courses. In this study, an industry-based air-conditioning (AC) unit is facilitated to prepare a case study to teach refrigeration cycles in the laboratory part of thermodynamics. All four components of the AC unit, which include a compressor, a condenser, an expansion valve, and an evaporator, are assembled on a single platform. In an actual application, the compressor and condenser are part of the outside unit while an evaporator and expansion valve would be located indoors. In the first phase of the case study, students analyze temperature and pressure data for the normal operation of the unit to understand the function of each component in the cycle. In addition, by using thermodynamics property tables, they determine enthalpy and entropy values at different stages of the process, generate a temperature versus entropy (T-s) diagram, and calculate the efficiency of the AC unit. In the second phase of the study, they are provided with temperature and pressure data collected for the cases corresponding to when there is a problem with the AC unit. They perform analysis of those cases. The examples of issues introduced include part of the condenser or evaporator coils being disabled or using a partially blocked air filter. The equipment used in the case study is modified by the manufacturer to simulate those issues. During data analysis, student teams are tasked with identifying the issue introduced by looking at the changes in temperature, pressure, and T-s diagram. This paper provides detailed information about the case study, data collection, and analysis. Copyright © 2022 by ASME.

CONSIDERATIONS FOR DEVELOPING AN ENGAGING MANAGEMENT CURRICULUM FOR UNDERGRADUATE ENGINEERING STUDENTS DURING COVID-19: A CASE OF OPERATIONS MANAGEMENT AT THE UNIVERSITY OF MANCHESTER

The rapid adoption of technology and digitization of work, which has affected every facet of life including pedagogy, has created an opportunity to develop novel ways to teach technical and management skills to students to make them industry ready. However, several studies have highlighted that students studying engineering related disciplines within higher educational institutions are often disconnected from the management units within their programme curriculum, irrespective of the level of complexity. Additionally, there are concerns that the recent shifts towards predominantly hybrid or online & blended learning (OBL) approach advocated by most institutions due to restrictions imposed by COVID-19 pandemic has further eroded the already exiguous interest levels. This study therefore attempts to understand how engineering students at a department within the University of Manchester perceive management units and the possible root causes of previously observed attitudes. The unit examined was Operations Management (MACE30461), which is mandatory for all final year undergraduates studying for graduate degrees in aerospace, civil and mechanical engineering. The fundamental rationales behind selecting this unit are its coverage of several disciplines and cohort size, with an average of approximately 350 registered engineering students per year over the last five years. To achieve the overarching aim of this study, data was innovatively obtained from five separate cohorts, through a popular continuous improvement technique - the Fishbone diagram (FBD). The benefits of this data collection approach is multi-faceted. Firstly, it reinforces learning and familiarity of the students with the applied tools, which is crucial to the achievement of the intended learning outcomes (ILOs). Secondly, it enhances direct extraction of root causes (RCs) of the identified limiters as well as their possible causal relationships. Out of approximately 1758 students that have been registered on this unit over five years, 962 returned their solutions to the exercise. As it would be very unrealistic to present all of the individual FBDs constructed by each student, a harmonised FBD was reconstructed based on all the identified RCs. The results of the study generally depict two overwhelming findings. Firstly, there is a general misconception of the meaning of engineering, as most students believe that engineering programmes should only encompass core technical elements such as thermodynamics, design, fluid mechanics, vibrations, etc. Secondly, majority of students find the contents of most management units offered to engineering students uninteresting, particularly because of a lack of well-established link between such contents and what they perceive as real engineering. The authors therefore argue for innovative teaching methods that embed tools that are coherent with core technical units through hybrid or OBL, which is both cost effective and practical given the prevailing pandemic environment. Copyright © 2022 by ASME.

Molecular docking analysis of novel quercetin derivatives for combating SARS-CoV-2

Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds had low toxicities and good absorption and solubility properties. The molecular docking results revealed that the propensity for binding to SARS-CoV-2 main protease is extraordinary. The results are remarkable not only for the binding energy values, which outperform several compounds in prior studies, but also for the number of hydrogen bonds formed. Compound 7a was capable of forming 10 strong hydrogen bonds as well as interact to the protein receptor with a binding energy of -7.79 kcal/mol. Therefore, these compounds should be highlighted in further experimental studies in the context of treating SARS-CoV-2 infection and its effects.

Atomic-level thermodynamics analysis of the binding free energy of SARS-CoV-2 neutralizing antibodies.

Understanding how protein-protein binding affinity is determined from molecular interactions at the interface is essential in developing protein therapeutics such as antibodies, but this has not yet been fully achieved. Among the major difficulties are the facts that it is generally difficult to decompose thermodynamic quantities into contributions from individual molecular interactions and that the solvent effect-dehydration penalty-must also be taken into consideration for every contact formation at the binding interface. Here, we present an atomic-level thermodynamics analysis that overcomes these difficulties and illustrate its utility through application to SARS-CoV-2 neutralizing antibodies. Our analysis is based on the direct interaction energy computed from simulated antibody-protein complex structures and on the decomposition of solvation free energy change upon complex formation. We find that the formation of a single contact such as a hydrogen bond at the interface barely contributes to binding free energy due to the dehydration penalty. On the other hand, the simultaneous formation of multiple contacts between two interface residues favorably contributes to binding affinity. This is because the dehydration penalty is significantly alleviated: the total penalty for multiple contacts is smaller than a sum of what would be expected for individual dehydrations of those contacts. Our results thus provide a new perspective for designing protein therapeutics of improved binding affinity.

A DFT study of vibrational spectra of 5-chlorouracil with molecular structure, HOMO-LUMO, MEPs/ESPs and thermodynamic properties.

The density functional theory calculation has been carried out for the analysis of 5-chlorouracil using DFT/Gaussian 09 with GAR2PED. Recorded experimental spectra for Raman and IR of 5-chlorouracil have been analyzed all fundamental vibrational modes using the outcome results of DFT at 6-311++G** of Gaussian 09 calculations and the GaussView 5.09. To help the analysis of vibrational modes, GAR2PED program has been used in the calculation of PEDs. The charge transfer properties of 5-chlorouracil have been analyzed using HOMO and LUMO level energy analysis. HOMO and LUMO energy gap study supports the charge transfer possibility in molecule. These have been made to study for reactivity and stability of heterocyclic molecules for the analysis of antiviral drugs against the new corona virus: COVID-19. Here, the smaller energy gap of 5-chlorouracil is more responsible for charge transfer interaction in the heterocyclic drug molecules and a reason of more bioactivity. The electron density mapping within molecular electrostatic potential plot and electrostatic potential plotting within iso-surface plot have been evaluated the charge distribution concept in the molecule as the nucleophilic reactions and electrophilic sites. These computations have been used to produce the molecular charges, structure and thermodynamic functions of biomolecule. This study has been made to all internal modes of chloro group substituent at pyrimidine ring of C5 atom. The splitting of frequencies has arisen in the two species for the normal distribution modes.

Interaction of GC376, a SARS-COV-2 MPRO inhibitor, with model lipid membranes

Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.

Virtualization of Laboratory Practices Using Visual Basic Excel

The COVID-19 pandemic and its related restrictions forced the reorganization of learning methodology and gave a central role to remote learning. Laboratory experiments are the most affected activity, and several alternatives were described. This work proposes to create calculation tools by simply programming in Visual Basic of Excel to emulate the data acquisition of specific laboratory experiments. The approach appears useful in experiments with a simple setup followed by data analysis. The experiment of gas volumetric properties allows fixing pressure and temperature conditions and measuring the occupied volume. The developed program emulates such operations and reports a computed volume. Further data reduction is the same in both procedures. Such a virtual experience was successfully used with groups of over 100 students. The results obtained were satisfactory compared with those obtained in the laboratory. Detailed analysis of the grades shows that acquired skills are comparable in both methodologies. Consequently, the virtual approach is a flexible option for remote laboratory teaching to complement traditional experimentation. Published 2022 by American Chemical Society and Division of Chemical Education, Inc.

A Computational Framework for Determining the Breadth of Antibodies Against Highly Mutable Pathogens

Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth” of a given antibody, an essential aspect of antibody design. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.

Theoretical studies, spectroscopic investigation, molecular docking, molecular dynamics and MMGBSA calculations with 2‐hydrazinoquinoline

• Spectral and theoretical characterization of 2-Hydrazinoquinoline. • Studies on Vibrational analysis, MEP surface, ELF diagram, NBO and NHO analysis. • Exploration of Fukui functions, Thermodynamic Properties and Hirshfield surface. • TD-DFT for UV–Vis studies along with FMO analysis. • ADME properties prediction and Molecular Docking with four different targets. • 200ns Molecular Dynamics Simulation followed by MMGBSA calculation. We report a comprehensive account on the theoretical and spectroscopic study of 2-hydrazinoquinoline. Computational studies have been performed using density functional theory (DFT) via B3LYP functional and 6-311++G (d,p) basis set. The theoretically predicted spectra showed good agreement with the experimentally obtained IR, NMR and UV spectra. TD-DFT provided information regarding the electronic transition probabilities. Calculation of the energy and structures of the FMO helped in understanding the stability, reactivity and other vital molecular properties. The NBO analysis afforded the insights on the various donor–acceptor interactions at the orbital level, that are responsible for stabilizing the molecule. The distribution of electron density across the molecule was studied using molecular electrostatic potential (MEP). The ELF studies were used to identify the electronic localization within the molecule. The pharmaco-kinetic properties along with the drug-likeness was analyzed as a part of understanding the therapeutic potential of the molecule. Molecular docking studies with four macromolecular targets (COVID-19 viral main protease, FABG4 enzyme, Cruzain and RIP2 Kinase) revealed reasonably good binding affinities. The stability of the best two docked-complexes were investigated using 200ns molecular dynamics simulation followed by effective free energy calculation using MMGBSA. [Display omitted] [ FROM AUTHOR]