Cation-π Interactions Research Articles

Functional Roles of the Charged Residues of the C- and M-Gates in the Yeast Mitochondrial NAD+ Transporter Ndt1p

Mitochondrial carriers transport organic acids, amino acids, nucleotides and cofactors across the mitochondrial inner membrane. These transporters consist of a three-fold symmetric bundle of six transmembrane α-helices that encircle a pore with a central substrate binding site, whose alternating access is controlled by a cytoplasmic and a matrix gate (C- and M-gates). The C- and M-gates close by forming two different salt-bridge networks involving the conserved motifs [YF][DE]XX[KR] on the even-numbered and PX[DE]XX[KR] on the odd-numbered transmembrane α-helices, respectively. We have investigated the effects on transport of mutating the C-gate charged residues of the yeast NAD+ transporter Ndt1p and performed molecular docking with NAD+ and other substrates into structural models of Ndt1p. Double-cysteine substitutions and swapping the positions of the C-gate charged-pair residues showed that all of them contribute to the high transport rate of wild-type Ndt1p, although no single salt bridge is essential for activity. The in silico docking results strongly suggest that both the C-gate motif mutations and our previously reported M-gate mutations affect gate closing, whereas those of the M-gate also affect substrate binding, which is further supported by molecular dynamics. In particular, NAD+ most likely interferes with the cation-π interaction between R303-W198, which has been proposed to exist in the Ndt1p M-gate in the place of one of the salt bridges. These findings contribute to understanding the roles of the charged C- and M-gate residues in the transport mechanism of Ndt1p.

Characterization and structural analysis of a leucine aminopeptidase using site-directed mutagenesis

Amp0279 (EC 3.4.11.24, GenBank: CP000817.1) is a Co2+-dependent leucine aminopeptidase from the Lysinibacillus sphaericus C3-41 genome. After analyses using molecular docking and spatial structure analysis, site-directed mutagenesis mutants were performed as Amp0279-R131E, Amp0279-R131H, Amp0279-R131A and Amp0279-E349D. The optimum pH of Amp0279-R131E was shifted from the original 8.5 to 7.5, and the overall electrostatic potential was shifted towards acidic. Compared with the original enzyme, the mutant proteins all gained better structural stability, especially the apparent melting temperature (Tm) of Amp0279-R131H increased from 41.8 to 45.5 °C. Morever, when protein was bound to the substrate, the Tm of Amp0279-R131E was increased by 7.3 °C and Amp0279-R131H increased by 5.4 °C, compared to the original enzyme. This is consistent with the results that the mutants acquired higher binding energies to the substrates, and an increase the hydrogen bonding force. In addition, the molecular docking of mutant and substrate revealed that the truncation of R131 contributes to the increase in the binding capacity of the substrate molecules to the active centre. In contrast, the presence of π-Cation interactions generated by R131 with the substrate has an important effect on the ability of Amp0279 to hydrolyse the substrate. This study demostrated that R131 is a key site for activity and stability, which is important in the future exploration of the functional structure of Amp0279.

Enhancing stability and physiological activity of Aronia melanocarpa L. anthocyanin by polysaccharides.

The existence of multiple phenolic hydroxyl groups in anthocyanins makes their structure unstable and leads to the degradation of anthocyanins. At present, there are few studies on the stability and physiological activity of Aronia melanocarpa L. anthocyanins by different polysaccharides. The present study investigated the effects of carboxymethyl cellulose (CMC), pectin and xanthan gum (XG) on the stability and biological activities of A. melanocarpa L. anthocyanins. The anthocyanins of A. melanocarpa L. (AAM) were successfully extracted from A. melanocarpa L. with an extraction rate of 3.07 mg g-1 by single factor and response surface experiments. The results of scanning electron microscopy and a multispectral technique showed that AAM-polysaccharides complex was combined by hydrogen bond, cation-π interaction and electrostatic interaction. The AAM-polysaccharides complex improved the retention rate of anthocyanins after treatment with light, heating, oxidant reducing agent, metal ions and preservatives compared to the results for AAM alone. Determination of DPPH· scavenging capacity, ABTS+ scavenging capacity and total reducing capacity indicated that the presence of polysaccharide could improve the antioxidant activity of AAM in vitro. The three polysaccharides combined with AAM showed higher binding ability to taurocholate and glycocholate compared to the AAM group, with the AAM-XG binding rate being the highest at 27.61% and 20.61%, respectively. The tyrosinase inhibition rate significantly increased with the incorporation of XG, reaching 72.22%. The stability and physiological activity of AAM were improved after the addition of CMC, pectin and XG in the simulated system, and the presence of XG showed greater advantages. The present study strongly suggests that anthocyanins driven by polysaccharides have a positive effect on the stability and physiological activity of anthocyanins and may also provide a research basis for the development of processing technology for anthocyanins in food. © 2024 Society of Chemical Industry.

An Ion Pair Receptor for Selective Solid-Liquid Extraction of LiCl.

We have synthesized a new ion pair receptor (2) consisting of a cone-calix[4]arene bearing a combination of ethyl esters and ethers as a cation binding site and a calix[4]pyrrole subunit acting as an anion binding site. Ion pair receptor 2 complexes LiCl, NaCl, and CsCl among alkali metal chloride salts with distinct complexation modes and affinities in 10% methanol-d4 in chloroform-d. For instance, relatively small Li+ and Na+ cations are bound to the oxygen atoms of the functionalized calix[4]arene lower rim with Cl- being hydrogen bonded to the calix[4]pyrrole NHs while the larger Cs+ cation is bound to the cone-shaped calix[4]pyrrole cavity via a π-cation interaction. By contrast, in the co-presence of all MCl salts (M = Li, Na, K, Rb, and Cs), receptor 2 binds LiCl with complete selectivity. Besides, receptor 2 is capable of extracting LiCl selectively into a chloroform or a dichloromethane organic phase from its solid source containing all other MCl salts.

Boosting Supramolecular Gelation Efficiency and Properties: Ionic Strength as a Key to Superior Hydrogels.

Controlling the minimum gelation concentration (MGC) of low molecular weight (LMW) hydrogelators is a key for modulating gel properties, such as mechanical strength, viscoelasticity, and stability, which are crucial for applications ranging from drug delivery to tissue engineering. However, tweaking the MGC under specific conditions, such as pH and/or temperature, poses a considerable challenge. Herein, we varied the ionic strength of buffer solutions using NaCl for several LMW hydrogelators, including Fmoc-Phe, Fmoc-Tyr, Fmoc-Trp, Fmoc-Met, and Fmoc-Cha, and assessed their gelation efficiency at pH 7.4 and ambient temperature. Interestingly, Fmoc-Phe demonstrated a ∼67% (3-fold) MGC reduction, from 0.24 to 0.08 wt %, at 500 mM NaCl, transforming it a "super hydrogelator" (MGC < 0.1 wt %), while Fmoc-Trp showed 60% MGC reduction. Higher ionic strength effectively shields the electrostatic repulsion between negatively charged (-COO-) groups on the Fmoc-Phe, promoting closer aggregation and more efficient self-assembly and allowing for gelation at lower concentrations. In contrast, Fmoc-Met, Fmoc-Cha, and Fmoc-Tyr precipitated in the presence of NaCl, suggesting that NaCl specifically modulates the MGC of Fmoc-amino acid gelators containing unsubstituted aromatic side chains. Furthermore, these results indicate that cation-π interactions likely play a role, alongside carboxylic acid neutralization. While Fmoc-Phe forms gels in the presence of other monovalent cations, it does not form a hydrogel in the presence of divalent (CaCl2) and trivalent (AlCl3), indicating that enhancement of hydrogelation is specific to monovalent cations. Although the fibrillar structure of Fmoc-Phe hydrogels remained consistent, addition of NaCl increased fibril stickiness, creating densely packed networks that modulate the mechanical strength. Unlike typical cases where increased ionic strength leads to precipitation, Fmoc-Phe gelation at high NaCl concentrations (150-500 mM) is significant, yielding a robust supramolecular hydrogel that remains stable in high ionic-strength environments. This outcome suggests that ionic strength could be a valuable factor to enhance the efficient gelation of LMW hydrogelators.

Physisorption of benzene on cation/silica clusters via cation-π interactions: Theoretical study

Interactions of a benzene molecule with four different silica clusters decorated with mono- and divalent cations (Li+, Na+, Mg2+) have been theoretically studied. By means of SAPT0 calculations, we have analyzed the changes in the energy components in dependence of hydrophobic or hydrophilic positions of adsorption, the size of the cluster studied or the cation used for the ’decoration’. It was found that adsorption of benzene on pristine silica clusters is mainly driven by electrostatic (∼37–43 %) and dispersion (∼37–55 %) forces. At the same time, cation-π interactions can be accounted for by significant electrostatic (∼20–50 %) and induction (∼24–54 %) energy terms. IGM analysis reveals the existence of cation-π and van der Waals interactions. The significant binding of benzene to the decorated silica surface (up to ∼ − 19.97, −29.63, − 93.82 kcal/mol for Na+, Li+, Mg2+, respectively) can pave a way for the sorption of a typical organic contaminant.

Ultralight and robust polyimide aerogels with tunable porous structures based on cation-π interactions for superior thermal insulation

Polyimide (PI) aerogels, renowned for their ultra-low density and exceptional porosity, exhibit substantial potential for thermal insulation applications. However, conventional freeze-drying method often produces irregular and large pore structures, which compromise the mechanical properties of PI aerogels and limit their practical applications. In this work, the enhanced PI-Cu aerogels by cation-π interactions are fabricated through the introduction of Cu ions and benzimidazole. The findings reveal that cation-π interactions facilitate the transformation of PI aerogels from two-dimensional layered structure to three-dimensional honeycomb structure characterized by smaller and more uniform pores, significantly reducing shrinkage and leading to ultra-light properties. Remarkably, a significant improvement of mechanical performance is also achieved after introducing cation-π interactions, even at a decreased density (0.046 g/cm3). Specifically, for samples with 3.5 wt% solid content, the yield strength and modulus of PI-Cu aerogels increase to 0.71 MPa and 13.58 MPa, respectively, representing improvements of 344 % and 520 % over pristine PI aerogels, which are superior to those of many other previously reported PI aerogels/foams with similar or even higher densities. Additionally, the toughness is significantly elevated from 13.5 MPa to 48.8 MPa. More importantly, after introducing cation-π interactions, the thermal insulation of PI-Cu aerogels are also improved with thermal conductivity decreasing from 0.04214 to 0.03997 W/m·K in axial direction and from 0.0399 to 0.03688 W/m·K in radial direction at 25°C. Interestingly, the thermal conductivity show only a slight increase under 180°C less than 0.05741 W/m·K in axial direction and 0.04923 W/m·K in radial direction owning to their exceptional thermal stability (Tg = 404 °C, T5%=524 °C). These exceptional properties position PI-Cu aerogels as promising candidates for diverse functional applications in the field of energy conservation.

Large-scale Conformational Changes of Diindole Functional Groups Driven by Cation-π Interactions and the Toughening Mechanism of Thermosets.

This is described that a new concept for the design of toughening supramolecular thermosets by incorporating diindole groups, which are functionalized via cation-π interactions in covalently crosslinked networks. Large-scale conformational changes of the diindole functional groups could occur under external forces, endowing the thermosets with excellent toughening properties.

Alkali cation-π interactions in aqueous systems, modulating supramolecular stereoisomerism of nanoscopic metal-organic capsules

Contrary to common chemical intuition, cation-π interactions can persist in polar, aqueous reaction solutions, rather than in dry non-coordinative solvent systems. This account highlights how alkali ion-π interactions impart distinctive structure-influencing supramolecular forces that can be exploited in the preparation of nanoscopic metal-organic capsules. The incorporation of alkali ions from polar solutions into molecular pockets promotes the assembly of otherwise inaccessible capsular entities whose structures are distinctive to those of common polyoxovanadate clusters in which {V=O} moieties usually point radially to the outside, shielding the molecular entities. The applied concept is exemplified by homologous {V20} and {V30} cages, composed of inverted, hemispherical {V5O9} units. The number and geometrical organization of these {V5O9} sub-units in these cages are associated with prevailing cation-π\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pi$$\\end{document} interactions and competing steric effects. The stereoisomers of these resulting nano-sized objects are comparable to Alfred Werner-type structural isomers of simple mononuclear complexes in-line with fundamental coordination chemistry principles.

Molecular Determinants for Guanine Binding in GTP-Binding Proteins: A Data Mining and Quantum Chemical Study.

GTP-binding proteins are essential molecular switches that regulate a wide range of cellular processes. Their function relies on the specific recognition and binding of guanine within their binding pockets. This study aims to elucidate the molecular determinants underlying this recognition. A large-scale data mining of the Protein Data Bank yielded 298 GTP-binding protein complexes, which provided a structural foundation for a systematic analysis of the intermolecular interactions that are responsible for the molecular recognition of guanine in proteins. It was found that multiple modes of non-bonded interactions including hydrogen bonding, cation-π interactions, and π-π stacking interactions are employed by GTP-binding proteins for binding. Subsequently, the strengths of non-bonded interaction energies between guanine and its surrounding protein residues were quantified by means of the double-hybrid DFT method B2PLYP-D3/cc-pVDZ. Hydrogen bonds, particularly those involving the N2 and O6 atoms of guanine, confer specificity to guanine recognition. Cation-π interactions between the guanine ring and basic residues (Lys and Arg) provide significant electrostatic stabilization. π-π stacking interactions with aromatic residues (Phe, Tyr, and Trp) further contribute to the overall binding affinity. This synergistic interplay of multiple interaction modes enables GTP-binding proteins to achieve high specificity and stability in guanine recognition, ultimately underpinning their crucial roles in cellular signaling and regulation. Notably, the NKXD motif, while historically considered crucial for guanine binding in GTP-binding proteins, is not universally required. Our study revealed significant variability in hydrogen bonding patterns, with many proteins lacking the NKXD motif but still effectively binding guanine through alternative arrangements of interacting residues.

Electric-Field Catalysis on Carbon Nanotubes in Electromicrofluidic Reactors: Monoterpene Cyclizations.

The control over the movement of electrons during chemical reactions with oriented external electric fields (OEEFs) has been predicted to offer a general approach to catalysis. Recently, we suggested that many problems to realize electric-field catalysis in practice under scalable bulk conditions could possibly be solved on multiwalled carbon nanotubes in electromicrofluidic reactors. Here, we selected monoterpene cyclizations to assess the scope of our system in organic synthesis. We report that electric-field catalysis can function by stabilizing both anionic and cationic transition states, depending on the orientation of the applied field. Moreover, electric-field catalysis can promote reactions which are barely accessible by general Brønsted and Lewis acids and field-free anion-π and cation-π interactions, and drive chemoselectivity toward intrinsically disfavored products without the need for pyrene interfacers attached to the substrate to prolong binding to the carbon nanotubes. Finally, interfacing with chiral organocatalysts is explored and evidence against contributions from redox chemistry is provided.

Visible light-promoted, catalyst-free synthesis of isoniazid azomethines: In vitro antioxidant activity, molecular docking, ADME and toxicity prediction

Green synthesis of biologically active molecules is essential for environmental sustainability, resource efficiency, reduced environmental impact, and compliance with regulations. It ensures a safer working environment, and fosters innovation in sustainable chemistry practices. In this context, we introduce an electron donor-acceptor (EDA)-mediated visible light-promoted, catalyst-free (VLCF) scalable synthesis of isoniazid azomethines. This synthesis encompasses the drug salizide and its analogues, which were subsequently evaluated for their antioxidant activities. Isoniazid azomethines 3e demonstrated superior activity compared to salizide and ascorbic acid, with an IC50 of 0.078 mg/mL in the hydrogen peroxide antioxidant assay. Specifically, 3e exhibited greater antioxidant properties (79.02 %) than isoniazid azomethine 3b (75.82 %), isoniazid azomethine 3d (62.2 %), isoniazid azomethine 3c (59.86 %), and isoniazid azomethine 3a (54.62 %). In the superoxide dismutase antioxidant assay, 3e was also identified as the most active, with a SOD activity level of 650 U/mg of protein, surpassing other compounds (3a-d) with SOD activity levels of 330, 560, 350, and 420 U/mg of protein, respectively. Molecular docking against horseradish peroxidase (1W4Y) showed compound 3e with the best binding energy (-6.561 kcal/mol), forming key hydrogen bonds (Asn135, Pro139) and a π-cation interaction with Arg38. These interactions suggest 3e may effectively inhibit hydrogen peroxide catalysis. The in silico assessment of the physicochemical properties, pharmacokinetics, and toxicology of synthesized compounds suggests that these compounds exhibit promising ADMET characteristics, with no identified toxicological concerns.

PH-Dependent Assembly and Stability of Toll-Like Receptor 3/dsRNA Signaling Complex: Insights from Constant pH Molecular Dynamics and Metadynamics Simulations.

The pH-dependent assembly of Toll-like receptors (TLRs), which triggers a threshold-like response, is a key principle in immune signaling. While crystallography has revealed the intricate structure of these assembly complexes, the mechanisms underlying their pH dependency remain unclear. Herein, constant pH simulations and metadynamics are employed to investigate the pH-dependent assembly and stability of the TLR3/dsRNA signaling complex. The findings demonstrate that system pH regulates complex assembly and stability by modulating the protonation and charge states of histidines. Histidines in TLR3 act as pH-dependent, positively charged binding sites that capture negatively charged dsRNA. Additionally, these histidines form a [H682⁺]-[E626⁻] dipole, facilitating the assembly of two TLR3 molecules into an antisymmetric dimer through dipole-dipole interactions. Surprisingly, TLR3 can shift the pKa values of key histidines from their model pKa of 6.5, increasing protonation likelihood and enhancing ligand binding. Notably, the aromatic residue Phe84, located within the dsRNA binding site [His39⁺-His60⁺-Phe84-His108⁺], alters the pKa of His60 through cation-π interactions with its protonated state. This study offers new insights into the molecular mechanisms underlying pH-dependent immune signaling via higher-order assemblies and suggests potential applications for histidine in self-assembling biomaterials.

Structure-based design and screening of hydrogel copolymer/Fe3O4 composite microspheres for magnetic solid phase extraction of bisphenol A from aqueous samples

It is of great significance to monitor bisphenol A (BPA) in the environment because of its potential environmental and health risks. However, the detection of trace or ultratrace BPA in complicated environmental samples is challenging due to the relatively low affinity and poor selectivity of existing adsorbents used in sample pretreatment. Herein, we report a high-affinity, low environment-dependent and strong interference-resistant abiotic affinity ligand, a N-methacryloyl-l-lysine-NH2 (MLys)-based hydrogel copolymer (HP 17) screened from a small focused polymer library engineered by incorporating various combinations and ratios of candidate functional monomers. The selection of these monomers was guided by molecular mechanism between BPA and the ligand-binding pocket of its estrogen receptors. The BPA–HP17 binding is mainly a synergistic effect of π-cation and hydrophobic interactions. The screened HP 17 has high adsorption capacity (349.4 mg/g) for BPA under wide pH (3.0–10.0) and ionic strength (0–150 mM) range. To improve its practicability, a hydrogel copolymer/Fe3O4 composite microspheres (Fe3O4@HP 17) was synthesized and applied for magnetic solid phase extraction–high-performance liquid chromatography (MSPE–HPLC) analysis of BPA in tap water, lake water and industrial effluents. The method shows wide linear range (2.5⁓100 ng/mL), high sensitivity (detection limit of 0.22 ng/mL even without further concentration after desorption), high accuracies (92.6⁓103.0 %) and good precisions (0.57⁓4.53 %), indicating a great potential of this material and method in the detection of trace or ultratrace BPA in complex environmental water samples.

Ultra-High Metal-Ion Selectivity Induced by Intramolecular Cation-π Interactions for the One-Pot Synthesis of Precise Heterometallic Architectures.

Heterometallic supramolecules, known for their unique synergistic effects, have shown broad applications in photochemistry, host-guest chemistry, and catalysis. However, there are great challenges to precisely construct heterometallic supramolecules rather than a statistical mixture, due to the limited metal-ion selectivity of coordination units. In particular, heterometallic architectures precisely encoded with different metal ions usually fail to form in a one-pot method when only one type of coordinated motif exists due to its poor metal-ion selectivity. Herein, we propose an effective intramolecular cation-π (ICπ) strategy and successfully constructed the heterometallic supramolecule Zn2Cu4L34 by the one-pot self-assembly of tritopic terpyridyl ligand L3 with Zn(II) and Cu(II), following a clear self-assembly mechanism in which only thermodynamic dimers ZnL12 and Cu2L22 were constructed with model ligands L1, L2, Zn(II) and Cu(II) with perfect self-sorting and an ultra-high metal-selectivity feature. The successful construction of the heterometallic supramolecule Zn2Cu4L34, in which the definite sequence of metal ions Zn(II) and Cu(II) is encoded in the one-pot method, will offer a novel approach to precisely construct heterometallic architectures.

Highly efficient thermal insulation polyimide foams enhanced by cation-π interactions

Highly efficient thermal insulation polyimide foams enhanced by cation-π interactions

Phase separation of chimeric antigen receptor promotes immunological synapse maturation and persistent cytotoxicity.

Major challenges of chimeric antigen receptor (CAR)-T cell therapy include poor antigen sensitivity and cell persistence. Here, we report a solution to these issues by exploiting CAR phase separation. We found that incorporation of an engineered Tcell receptor CD3ε motif, EB6I, into the conventional 28Z or BBZ CAR induced self-phase separation through cation-π interactions. EB6I CAR formed a mature immunological synapse with the CD2 corolla to transduce efficient antigen and costimulatory signaling, although its tonic signaling remained low. Functionally, EB6I CAR-T cells exhibited improved signaling and cytotoxicity against low-antigen tumor cells and persistent tumor-killing function. In multiple primary and relapsed murine tumor models, EB6I CAR-T cells exerted better antitumor functions than conventional CAR-T cells against blood and solid cancers. This study thus unveils a CAR engineering strategy to improve CAR-T cell immunity by leveraging molecular condensation and signaling integration.

Squid-Inspired Anti-Salt Skin-Like Elastomers With Superhigh Damage Resistance for Aquatic Soft Robots.

Cephalopod skins evolve multiple functions in response to environmental adaptation, encompassing nonlinear mechanoreponse, damage tolerance property, and resistance to seawater. Despite tremendous progress in skin-mimicking materials, the integration of these desirable properties into a single material system remains an ongoing challenge. Here, drawing inspiration from the structure of reflectin proteins in cephalopod skins, a long-term anti-salt elastomer with skin-like nonlinear mechanical properties and extraordinary damage resistance properties is presented. Cation-π interaction is incorporated to induce the geometrically confined nanophases of hydrogen bond domains, resulting in elastomers with exceptional true tensile strength (456.5 ± 68.9MPa) and unprecedently high fracture energy (103.7 ± 45.7kJ m-2). Furthermore, the cation-π interaction effectively protects the hydrogen bond domains from corrosion by high-concentration saline solution. The utilization of the resultant skin-like elastomer has been demonstrated by aquatic soft robotics capable of grasping sharp objects. The combined advantages render the present elastomer highly promising for salt enviroment applications, particularly in addressing the challenges posed by sweat, in vivo, and harsh oceanic environments.

Enzymatic hydrolysis of buffalo casein enhances DPP-4 inhibition: structural modifications and bioactive peptide identification

Dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for the rapid degradation of incretin hormones, plays a pivotal role in blood glucose regulation, and its inhibition serves as an effective strategy for maintaining glucose homeostasis. The aim of this study was to investigate the effect of enzymatic hydrolysis on the structure of buffalo casein and its DPP-4 inhibitory activity. Results demonstrated that Flavorzyme effectively hydrolyzed buffalo casein, as evidenced by scanning electron microscopy and electrophoretic analysis, with the degree of hydrolysis reaching its maximum value (20.05 ± 0.14%) after 3 h. The results of circular dichroism spectra, as well as endogenous and exogenous fluorescence spectra, indicated significant alterations in the secondary and tertiary structures of buffalo casein following enzymatic hydrolysis. Additionally, the DPP-4 inhibitory effect of buffalo casein was found to increase with longer hydrolysis times. The hydrolysate obtained after 3 h of hydrolysis demonstrated the highest level of inhibition, with a half-maximal inhibitory concentration (IC50) value of 1.04 mg/mL. The DPP-4 inhibitory peptide YPFPGPIPN, with an IC50 value of 0.88 mg/mL, was identified in the 1-3 kDa fraction of the 3-h hydrolysate. This peptide interacted with the active site of DPP-4 via hydrogen bonds, hydrophobic interactions, salt bridges, and π-cation interactions. This study offers a novel scientific foundation for the development of functional antidiabetic foods derived from buffalo casein.

Substituted Indole Derivatives against Leucine Transporter (LeuT) as SSRI Antidepressant: Molecular Dynamics Study

Molecular docking and molecular dynamics on substituted indole derivatives-Leucine Trasporter had been performed. Indole derivatives with methoxy and fluorine group are chosen and specific amino acid residue Arg30 and Asp404 are π-alkyl and π-cation interactions. The suggested molecule containing methoxy groups has an RMSD value of 1.95 Å, a binding energy of-4.00 kcal mol-1, and an inhibition constant of 1.17 μM. The hypothesized fluorine-containing compound's RMSD value, binding energy, and inhibition constant were each 1.88 Å; -5.97 kcal mol-1; and 41.88 μM, respectively. The substituted indole derivative with the methoxy group was stable, according to the findings of a 200-ns molecular dynamics simulation, while the substituted indole derivative with the fluorine group was less stable. Based on the examination of RMSD, RMSF, RoG, the quantity of hydrogen, and the level of contact stability of the ligands with the particular amino acid residues for the antidepressant drug, the dynamical interaction of ligands against LeuT was determined.