Probable Site Research Articles

Factors influencing the global invasion of the South American weedy species Praxelis clematidea (Asteraceae): a niche shift and modelling-based approach

Abstract Praxelis clematidea is a relatively unknown herb native to South America that has spread globally over the past four decades. In this study, we integrate ecological niche modelling (ENM) and niche shift analyses to understand its distribution, test niche conservatism hypotheses, and identify potential invasion sites under different climate change scenarios. In its native range, P. clematidea prefers climates with mild annual temperatures and winters. This species shows a great potential to continue spreading. Probable invasion sites include northern South America, Central America, India, Southeast Asia, and Africa. Future climate projections suggest increase of potential distribution in tropical regions and decrease in temperate areas. Niche conservatism was evident, although invaded areas in Asia and Australia showed slight niche expansion towards warmer climates, probably explained by ecological factors such as competition. Our results show that integrating occurrences from both native and invaded ranges in ENM models enhances predictability, even when niche is conserved. The combination of niche shift studies and ENM provides better insight into species invasion dynamics, resulting in the recognition of high-risk invasion areas that combined with the rapid access to new occurrences provided by citizen science platforms can result in early detection and lead to better management strategies.

Local Morphologic and Hemodynamic Analyses for the Prediction of Abdominal Aortic Aneurysm Rupture Based on Patient-Specific CTA and Computational Modeling.

Extensive research has focused on the evaluation of rupture risks in abdominal aortic aneurysms (AAAs) through comprehensive morphologic and hemodynamic analyses, primarily considering the AAA as a whole entity. This study tried to identify the high-risk rupture sites of AAAs more precisely before the fatal process based on morphologic and hemodynamic analyses at the local segment. Computed tomography angiography of a specific AAA patient was conducted at the follow-up 4 months before rupture, 1 day before rupture, the day of the rupture, and 15 days after endovascular aortic repair. The evolution of local morphology and the hemodynamic characteristics at these critical timepoints were investigated based on patient-specific reconstructions and computational fluid dynamics. The morphologic and hemodynamic parameters of the rupture region vary continuously in the process of AAA development and rupture. The surface area and volume of the rupture segment were gradually enlarged at the follow-up 4 months before rupture (47.33 cm2; 67.35 mL), 1 day before rupture (57.23 cm2; 85.24 mL), and on the day of the rupture (62.41cm2; 104.73ml). A prominent decrease in time-averaged wall shear stress and velocity for the rupture segment is observed. The percentages of the lowest time-averaged wall shear stress (<0.1 Pa) area are increased in the AAA region (20.42%, 33.85%, and 53.00%, separately). The results based on precisely rebuilt geometries for the complete follow-ups of patient-specific computed tomography angiography demonstrate that notable morphologic and hemodynamic evolutions have occurred in the local segment of the AAA, which was further proved at the rupture site. The significant changes occurring at the local segment may provide valuable information for the evaluation of aneurysm rupture risk and locate the most probable site of rupture. Capturing the entire process of AAA rupture through CTA imaging is a rare occurrence in clinical practice. The evolution of morphology and hemodynamic characteristics observed in the illustrated results provides valuable insights for clinicians to monitor the state of AAA from a different perspective. These findings suggest that variations in morphology and hemodynamics within the local segment of the AAA might serve as an alternative approach for predicting the rupture risk of AAA.

Diagnosing Autoimmune Bullous Diseases—An Indian Perspective

Abstract Introduction: Autoimmune bullous diseases (AIBDs) are a group of illnesses characterized by autoantibodies targeting adhesion molecules in the skin and mucosa. Accurate diagnosis of the specific subtype of AIBD is crucial for effective management and predicting prognosis, especially in cases with an increased risk of malignancy. However, differentiating between subtypes can be challenging due to overlapping symptoms. Overview of diagnostic tests: Direct immunofluorescence microscopy (DIF) detects in vivo bound antibodies in perilesional tissue biopsies and provides details about the probable site of autoantibody deposition within the skin/mucosae, immunoglobulin type, and pattern of antibody deposition. Indirect immunofluorescence (IIF) microscopy with organ substrate is a minimally invasive serological test that detects circulating autoantibodies. Enzyme-linked immunosorbent assay (ELISA) quantifies serum autoantibodies against specific autoantigens. Quantitative ELISA is useful for diagnosis, monitoring therapy, and assessing disease activity. Commercially available ELISA kits, including the multi-variant ones, can detect antibodies associated with AIBDs. BIOCHIP is a technique based on IIF that offers a sensitive and specific diagnostic alternative to ELISA. It uses microarrays with multiple antigenic substrates to simultaneously screen common AIBDs. The BIOCHIP slides contain different substrates, allowing the identification of multiple types of autoantibodies in a single test. Indian context: While these diagnostic tests offer valuable insights into target antigens, antibody patterns, and disease subtypes, it is important to note that the availability of these tests is limited in most centers across India. This limitation can be attributed to factors such as the relatively higher cost of these investigations, challenges related to the stability of immuno-reactants, and a shortage of trained personnel capable of performing such tests. Conclusion: This review discusses the diagnosis of AIBDs based on resources available in India, as of today. It also provides with practically applicable diagnostic algorithms for pragmatic diagnosis of AIBDs in Indian scenario.

Pressure-Dependent Shape and Edge Configurations of MoS2 by Kinetic Monte Carlo Simulation.

Understanding the influence of precursor pressures is crucial for optimizing the properties of MoS2 grown through the chemical vapor deposition (CVD) process. In this study, we use kinetic Monte Carlo (KMC) simulations to investigate how varying the pressures of molybdenum (PMo) and sulfur (PS) impacts the structural properties of MoS2, such as grain shape and edge configurations. The simulations differentiate three distinct regimes─growth, steady-state, and etching─each defined by specific PMo, PS, and the most probable atomic sites for filling or etching. We further explore how these regimes influence the atomic configuration of MoS2, particularly the formation of different edge structures like sulfur zigzag (ZZS), molybdenum zigzag (ZZMo), and their respective derivatives. A pressure diagram based on the equations of state and most probable atomic sites was constructed for each regime and validated by comparing predicted ZZ-derived edges to experimental observations. Additionally, the study examines the impact of etching on various line defects, providing insights into the evolution of the MoS2 edges during the CVD process. These findings underscore the importance of controlling both growth and cessation phases in the CVD process to customize edge configurations, with significant implications for chemical functionalization, catalysis, and the electronic properties of transition metal dichalcogenides.

Spectroscopic characterization and investigation of reactive properties of 6-Chloro-N-(3-iodo-4-methylphenyl)-pyrazine-2-carboxamide by DFT calculations, with molecular docking and molecular dynamic study

The spectral characterization of 6-Chloro-N-(3-iodo-4-methylphenyl)-pyrazine-2-carboxamide (CIMPPC) was executed by FT-IR and FT-Raman spectroscopic methods and density functional theory (DFT) computations have been carried using B3LYP/gen method. On the basis of potential energy distribution (PED), the vibrational assignments of the wavenumbers were proposed. NBO analysis was performed to study donor acceptor interactions. Halogen substitution results in increase in the µ (chemical potential) value in comparison with the parent molecule, which is a minimum. Halogen substitution also results a decrease in electrophilicity index. Fundamental reactive properties of the title molecule are investigated by MEP analysis. Visualization of ALIE and Fukui functions evaluated the most probable sites for electrophilic attacks. Exposure of the CIMPPC towards autoxidation and hydrolysis is evaluated using BDE and RDF. The compatible nature of the compound is investigated through the Hildebrand solubility parameter. 6-Chloro-N-(3-iodo-4-methylphenyl)-pyrazine-2-carboxamide exhibit inhibitory activity against the anti-inflammatory receptor transient receptor potential cation channel.

Spectroscopic, quantum chemical and molecular docking studies of N-((anthracen-9-yl) methylene-2-methyl benzenamine): a potent probe to lipid bilayer systems

ABSTRACT A new synthesized Schiff base, N-((anthracen-9-yl) methylene-2-methyl benzenamine) (AMMB), was prepared from o-toluidine and 9-anthracenecarboxaldehyde. The structure of the compound was confirmed by single crystal X-ray diffraction and characterized through various analytical tools such as high resolution mass, 1H and 13C NMR, infrared, UV-vis and elemental composition analysis. The molecular geometries of AMMB were optimized by means of DFT/B3LYP/6311-G++ (d,p) basis set. The optimized geometric parameters of the compound were concordant with the single crystal structure. The optimized structure was utilized in comparison of experimental FT-IR with calculated frequency calculation. TD-DFT analysis was performed to compute the electronic absorption of the compound. SCF-GIAO was employed to compute 1H and 13C NMR, which was consistent with the experimental results. Additionally, NLO, NBO, MEP and global reactivity parameters were also computed using the same level of theory. Hirshfield surface analysis, fingerprint plot and energy frameworks were presented to explore the intermolecular interactions within the crystal. Molecular docking study was carried out to predict the probable binding site of AMMB into lipid bilayers such as DMPC, DPPC, POPC, DLPE, DOPC and POPE. The molecular docking analysis of AMMB showed complex formation with binding affinity energy ranging from −9.3 to −3.4 kcal/mol.

Assembly of a Heterobimetallic Fe/Mn Cofactor in the para-Aminobenzoate Synthase Chlamydia Protein Associating with Death Domains (CADD) Initiates Long-Range Radical Hole-Hopping.

Chlamydia protein associating with death domains (CtCADD) is involved in the biosynthesis of p-aminobenzoic acid (pABA) for integration into folate, a critical cofactor that is required for pathogenic survival. CADD activates dioxygen and utilizes its own tyrosine and lysine as synthons to furnish the carboxylate, carbon backbone, and amine group of pABA in a complex multistep mechanism. Unlike other members of the heme oxygenase-like dimetal oxidase (HDO) superfamily that typically house an Fe2 cofactor, previous activity studies have shown that CtCADD likely uses a heterobimetallic Fe/Mn center. The structure of the Fe2+/Mn2+ cofactor and how the conserved HDO scaffold mediates metal selectivity have remained enigmatic. Adopting an in crystallo metalation approach, CtCADD was solved in the apo, Fe2+2, Mn2+2, and catalytically active Fe2+/Mn2+ forms to identify the probable site for Mn binding. The analysis of CtCADD active-site variants further reinforces the importance of the secondary coordination sphere on cofactor preference for competent pABA formation. Rapid kinetic optical and electron paramagnetic resonance (EPR) studies show that the heterobimetallic cofactor selectively reacts with dioxygen and likely initiates pABA assembly through the formation of a transient tyrosine radical intermediate and a resultant heterobimetallic Mn3+/Fe3+ cluster.

Into the Groove: A Multitechnique Insight into the DNA–Vemurafenib Interaction

This study explores the interaction between Vemurafenib (VEM), a potent BRAF inhibitor, and calf thymus DNA (ctDNA) using a comprehensive array of biophysical and computational techniques. The primary objective is to understand the potential off-target effects of VEM on DNA, given its established role in melanoma therapy targeting the BRAF V600E mutation. The investigation employed methods such as ultraviolet–visible absorption spectroscopy, steady-state fluorescence, circular dichroism, isothermal titration calorimetry, and advanced molecular dynamics simulations. The results indicate that VEM interacts with DNA primarily through a minor groove-binding mechanism, causing minimal structural disruption to the DNA double helix. Viscosity measurements and melting temperature analyses further confirmed this non-intercalative mode of binding. Calorimetry data revealed an exothermic, thermodynamically favorable interaction between VEM and ctDNA, driven by both enthalpic and entropic factors. Finally, computer simulations identified the most probable binding site and mode of VEM within the minor groove of the nucleic acid, providing a molecular basis for the experimental findings.

Lateral node metastasis in low rectal cancer as a hallmark to predict recurrence patterns.

Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status. We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival. Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively). Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved.

Molecular Docking Studies of Synthesized Pyridazinone Scaffolds as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Pyridazinone derivatives, 6-aryl-pyridazinone (2a–f) and 2-(N-substituted)-6-aryl-pyridazinone (3a–h) derivatives were synthesized and assessed for cytotoxicity action using brine shrimp assessment method and in silico molecular studies. In silico molecular study of pyridazine derivatives used as NNRTIs and Doravirine is used as reference drug. The compounds were investigated for docking modes onto probable binding sites with HIV reverse transcriptase. The majority of these demonstrated favorable binding interactive connections with the active receptor domain. The majority of the compounds exhibited a remarkable docked binding affinity score when compared with the reference drugs. Among the synthesized pyridazine derivatives, compounds 3a and 3c–h exhibited a good docking score. For the designed compounds, in silico ADME assessment indicated the favorable physicochemical properties to be a suitable drug candidate. The synthesized compounds could serve as a novel alternative in designing safe and effective anti-HIV options with reverse transcriptase inhibitor potential. In the cytotoxicity study, all the compounds were evaluated at dose levels 10, and 20 (μg/mL), and potassium dichromate was used as a reference. Compounds 2c and 2e have shown potent lethality through LC50 2.23 and 3.20 μg respectively. Various compounds, including 2a, 2b, 2d, and 2f have demonstrated significant cytotoxicity. Their LC50 values are 7.58, 6.76, 8.91, and 4.46 μg, respectively. Additionally, compounds 3b and 3d exhibited potent lethality with LC50 values of 4.023 and 4.20 μg. Other compounds, namely 3g, 3f, 3c, 3h, 3a, and 3e, displayed noteworthy cytotoxicity ability13.91, 12.58, 11.91, 11.76, 10.58, 9.76, and 7.46 μg, respectively having LC50 values. This study supports the use of in silico molecular design and the brine shrimp bioassay as a suitable, reliable, and simple method for assessing the bioactivity of compounds. It provides further evidence for their use in medicine.

Probing the interaction mechanisms of lipid nanoparticle-encapsulated mRNA with surfaces of diverse functional groups: Implication for mRNA transport

The transport of mRNA plays an indispensable role in vaccine drug delivery and emerging therapies. The attachment of lipid nanoparticle encapsulating mRNA (mRNA-LNP) to biological and engineering surfaces is determined by their intermolecular and surface interactions. In this work, the interactions between mRNA-LNP and surfaces with various functional groups were investigated using atomic force microscopy. The results show that mRNA chains are coiled in LNPs, and the surface charges of mRNA are screened by the surrounding lipid molecules. Approach force curves demonstrate that the steric repulsion varies with functional groups. Force mapping reveals that the intermolecular interactions, i.e., hydrogen bonding and electrostatic interaction, contribute to the adhesion. The –OH group is suggested as the most probable binding site for mRNA-LNP attachment. This work provides new insights into mRNA transport mechanisms at biological and engineering surfaces, with useful implications for designing novel nanocarriers and developing functional surfaces for biological applications.

An Innovative Bio-Vehicle for Resveratrol and Tocopherol Based on Quinoa 11S Globulin-Nanocomplex Design and Characterization.

Nanocomplexes, which possess immense potential to function as nanovehicles, can link diverse ligand compounds. The objective of the present study was to design and characterize resveratrol (RSV)- and tocopherol (TOC)-loaded 11S quinoa seed protein nanocomplexes. Firstly, molecular docking was performed to describe the probable binding sites between protein and ligands, and binding energies of -5.6 and -6.2 kcal/mol were found for RSV and TOC, respectively. Isothermal titration calorimetry allowed us to obtain the thermodynamic parameters that described the molecular interactions between RSV or TOC with the protein, finding the complexation process to be exothermic and spontaneous. 11S globulin intrinsic fluorescence spectra showed quenching effects exerted by RSV and TOC, demonstrating protein-bioactive compound interactions. The application of Stern-Volmer, Scatchard, and Förster resonance energy transfer models confirmed static quenching and allowed us to obtain parameters that described the 11S-RSV and 11S-TOC complexation processes. RSV has a higher tendency to bind 11S globulin according to ITC and fluorescence analysis. Secondly, the protein aggregation induced by bioactive compound interactions was confirmed by dynamic light scattering and atomic force microscopy, with diameters <150 nm detected by both techniques. Finally, it was found that the antioxidant capacity of a single 11S globulin did not decrease; meanwhile, it was additive for 11S-RSV. These nanocomplexes could constitute a real platform for the design of nutraceutical products.

An extensive in silico analysis of missense mutations of the human AIMP2 gene

HLD17 (Hypomyelinating Leukodystrophy 17) is an inherited white matter disorder characterized by insufficient myelin production due to biallelic loss of function mutations in the aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) gene. In silico analysis of SNVs (single nucleotide variants) in the AIMP2 gene is an efficient and cost-effective method for analyzing and predicting the impact of mutations on protein function and disease pathophysiology.The study used dbSNP and Ensembl databases to obtain data on 343 nonsynonymous single nucleotide variants (nsSNVs) in the human AIMP2 gene. Six prediction algorithm tools were used to assess the effects of these nsSNVs on AIMP2's functions and structures. Results showed that 18 nsSNVs were located within functional domains, while 10 nsSNVs led to decreased protein stability. The structural and functional properties of the AIMP2 protein were investigated using databases such as Predict Protein, Mutpred2, and HOPE. ConSurf analysis provided information about conserved nsSNVs. GeneMANIA and STRING software tools were used to predict interactions between gene-gene and protein-protein, respectively. Phyre2 and I-TASSER web servers were used to predict the 3D structures of wild-type and mutant proteins.In addition, having the challenge of probable post-translational modification sites in the AIMP2, we made predictions using various bioinformatics tools. Consecuently, three minor mutations (L138Q, V161E, and I188N) and five major mutations (C23S, D121G, I122S, P128S, and W268S) were found to affect the AIMP2 protein's structure or function. Anyway, These mutations need to be further studied and confirmed through experimental investigation and GWAS studies.

Theoretical Study of the Regioselectivity of Some Monomers: Chitin and Chitosan

Biopolymers have become more and more attractive nowadays for both experimental and theoretical studies because of their importance in our daily life. In this contribution, the electronic properties and reactivity behavior of some biomonomers; chitin and chitosan have been thoroughly investigated theoretically using density functional theory (DFT) B3LYP/6-31G(d) level of theory. The regioselectivity of these molecules has been rationalized by using both Fukui and Parr indices in order to explain and show the most probable sites to be attacked towards nucleophiles and electrophiles. For the three studied monomers, the oxygen and nitrogen atoms were found to be the most reactive sites. Parr functions and Fukui functions found to be complementary while explaining the possible regioselectivity.

A computational DFT study of Imidazolium based Ionic liquids: binding energy calculation with different anions using Solvation Model

Basic knowledge of chemical events in the gaseous or liquid phase, as well as on surfaces, is required to determine the macroscopic process. The structure of ionic liquids were investigated using quantum chemistry. Cation and anion can bond together, according to the findings. Their binding and interaction energies reveal that they are produced by hydrogen bonds. The mechanism of a room temperature ionic liquid, such as [BMIM][Cl] (1-butyl-3-Methylimidazolium chloride) monomer, was studied using Density functional theory (DFT) computations using the modern continum solvation model (IEFPCM-SMD). Ionic liquid [IL] contains both anions and cations, allowing for greater intermolecular interactions. By analyzing the relative minimum energy of [BMIM][Cl] in the presence and absence of water, we were able to establish the minimum energy structures and probable Cl anion binding sites in [BMIM][Cl] ionic liquid. We have found that all 1-butyl-3-methylimidazolium halide ILs investigated had trans conformations due to the butyl group’s dihedral angles. GUB JOURNAL OF SCIENCE AND ENGINEERING, Vol 9(1), 2022 P 66-70

Cumulative phylogenetic, sequence and structural analysis of Insulin superfamily proteins provide unique structure-function insights.

The insulin superfamily proteins (ISPs), in particular, insulin, IGFs and relaxin proteins are key modulators of animal physiology. They are known to have evolved from the same ancestral gene and have diverged into proteins with varied sequences and distinct functions, but maintain a similar structural architecture stabilized by highly conserved disulphide bridges. The recent surge of sequence data and the structures of these proteins prompted a need for a comprehensive analysis, which connects the evolution of these sequences (427 sequences) in the light of available functional and structural information including representative complex structures of ISPs with their cognate receptors. This study reveals (a) unusually high sequence conservation of IGFs (>90 % conservation in 184 sequences) and provides a possible structure-based rationale for such high sequence conservation; (b) provides an updated definition of the receptor-binding signature motif of the functionally diverse relaxin family members (c) provides a probable non-canonical C-peptide cleavage site in a few insulin sequences. The high conservation of IGFs appears to represent a classic case of resistance to sequence diversity exerted by physiologically important interactions with multiple partners. We also propose a probable mechanism for C-peptide cleavage in a few distinct insulin sequences and redefine the receptor-binding signature motif of the relaxin family. Lastly, we provide a basis for minimally modified insulin mutants with potential therapeutic application, inspired by concomitant changes observed in other insulin superfamily protein members supported by molecular dynamics simulation.

Development of a novel sensory material for rapid detection of mercury ions in various water sources: Solution and solid-state analysis

A xanthene propane nitrile-based sensor material was successfully prepared, and an attempt towards the preparation of polymer bead form was made for the sensitive or selective detection of mercury ions (Hg2+) in water. The sensor material in solution as well as in polymeric form showed amazing selectivity over other added metal ions with a naked eye color change, UV visible spectral and fluorescence spectral change, and a rapid and excellent color change from colorless to purple. The 1H NMR study exposed the probable binding site of the probe with the added mercury ion. In this study, the imine nitrogen and the C = O interact with the mercury ion, resulting in the ring opening of lactam with a vivid color change. The EDTA test was done to verify the reversible behavior of the probe and confirmed its reversibility by UV–visible and fluorescence spectral studies. The polymer bead made using this probe can be used as a tool for monitoring mercury ions in real time in different sources of water samples. The sensor molecule itself senses the mercury ion in its solid state by simple grinding and changes its color from pale yellow to deep purple. The sensor color change response is very rapid towards mercury detection, which is confirmed by the prepared test strip.

A Comprehensive Computational Study on the Thermodynamics and Kinetics of Tetrahydrobiopterin Regeneration Process.

One of the most crucial enzymatic cofactors in the human body is tetrahydrobiopterin, which is acquired through biological synthesis and self-regeneration. During this regenerative process, it undergoes oxidation, deprotonation, further oxidation, and subsequent deprotonation, resulting in the formation of quinonoid-dihydrobiopterin, which then undergoes tautomerization to yield dihydrobiopterin. This study presents the thermodynamic and kinetic properties associated with each stage of the regeneration process using theoretical calculations. The redox potentials for oxidation steps and the pKa values for deprotonation steps are determined employing the Born-Haber cycle and the direct change of free energy in implicit solvent models. The redox metabolites are characterized and confirmed from their calculated absorption spectra using the time-dependent density functional theory method. For the tautomerization steps, an IRC calculation is executed, and rate constants are computed using Eyring's Transition State Theory (TST). The tunnelling probability of the H atom during the tautomerization process is incorporated using Wigner's tunnelling correction in the calculation of the rate constant. Notably, we identify the N3 atom as the most probable deprotonation site for H3B+ and predict its geometry based on our calculations. Furthermore, we elucidate the spectral properties of intermediates involved in the regeneration process, highlighting key electronic transitions responsible for their excitations. Our results indicate that each step of tautomerization occurs along vibrational bending modes. We have observed that these tautomerization processes have high activation energies by optimising transition states. Additionally, considering tunnelling correction can significantly affect the reaction rates associated with these processes. These results provide a comprehensive understanding of the thermodynamics and kinetics of the regeneration process of tetrahydrobiopterin, which will help in the modulation of its biological activity.

Investigating the Taenia solium Fatty Acid Binding Protein Superfamily for Their Immunological Outlook and Prospect for Therapeutic Targets.

Taenia solium, like other helminthic parasites, lacks key components of cellular machinery required for endogenous lipid biosynthesis. This deficiency compels the parasite to obtain all of its lipid requirements from its host. The passage of lipids across the cell membrane is tightly regulated. To facilitate effective lipid transport, the cestode parasite utilizes certain lipid binding proteins called FABPs. These FABPs bind with the lipid ligands and allow the transport of lipids across the membranes and into the cytosol. Here, by integrating a computational with homology protein prediction tools, we had identified five FABPs in the T. solium proteome. We confirmed their presence by RNA expression analysis of respective genes from the parasite's cysticerci transcript. During the molecular modeling and MD simulation studies, two of them, TsM_000544100 and TsM_001185100, were most stable. Furthermore, they had a robust interaction with the IgG1 molecule, as evidenced by MD simulation. In addition, by employing in silico screening, we had identified potential ligand interacting residues that are present on the probable druggable site. In combination with in vitro cysticidal assays, enalaprilat dihydrate showed efficacy against cysticerci, which suggests that FABPs play a significant role in the cysticercus life cycle. Together, we provided a detailed distribution of all FABPs expressed by T. solium cysticerci and the critical role of TsM_001185100 in cysticercus viability.

Molecular Insights into the Effect of Cholesterol on the Binding of Bicarbonate Ions in Band 3 Protein.

Band 3, or anion exchanger 1 (AE1), is one of the indispensable transmembrane proteins involved in the effective respiratory process of the human body and is primarily responsible for the exchange of bicarbonate and chloride anions across the plasma membrane of erythrocyte. However, the molecular mechanism of ion transport of Band 3 is not completely understood, yet. In this work, we systematically investigate the key binding sites of bicarbonate ions in Band 3 and the impact of cholesterol (CHOL) in lipid bilayers on bicarbonate ion binding using all-atom molecular dynamics (MD) simulations. We examine the dynamics of interactions of bicarbonate ions with Band 3 in the microsecond time scale and calculate the binding free energy of the anion in Band 3. The results indicate that the residue R730 of Band 3 is the most probable binding site for bicarbonate ions. CHOL enhances the bicarbonate ion binding by influencing the conformational stability of Band 3 and compressing the volume of the Band 3 cavity. These findings provide some insights into the bicarbonate ion binding in Band 3 and are helpful for understanding the anion exchange of Band 3.