Total Binding Energy Research Articles

In Silico Drug Repurposing Approach: Investigation of Mycobacterium tuberculosis FadD32 Targeted by FDA-Approved Drugs.

Background: Despite the enormous efforts made towards combating tuberculosis (TB), the disease remains a major global threat. Hence, new drugs with novel mechanisms against TB are urgently needed. Fatty acid degradation protein D32 (FadD32) has been identified as a promising drug target against TB, the protein is required for the biosynthesis of mycolic acids, hence, essential for the growth and multiplication of the mycobacterium. However, the FadD32 mechanism upon the binding of FDA-approved drugs is not well established. Herein, we applied virtual screening (VS), molecular docking, and molecular dynamic (MD) simulation to identify potential FDA-approved drugs against FadD32. Methodology/Results: VS technique was found promising to identify four FDA-approved drugs (accolate, sorafenib, mefloquine, and loperamide) with higher molecular docking scores, ranging from −8.0 to −10.0 kcal/mol. Post-MD analysis showed that the accolate hit displayed the highest total binding energy of −45.13 kcal/mol. Results also showed that the accolate hit formed more interactions with FadD32 active site residues and all active site residues displayed an increase in total binding contribution. RMSD, RMSF, Rg, and DCCM analysis further supported that the presence of accolate exhibited more structural stability, lower bimolecular flexibility, and more compactness into the FadD32 protein. Conclusions: Our study revealed accolate as the best potential drug against FadD32, hence a prospective anti-TB drug in TB therapy. In addition, we believe that the approach presented in the current study will serve as a cornerstone to identifying new potential inhibitors against a wide range of biological targets.

Establishing the mutational effect on the binding susceptibility of AMG510 to KRAS switch II binding pocket: Computational insights

After decades of leaving patients with limited treatment options due to the ‘undruggability’ of Kirsten rat sarcoma, the kernel was finally cracked with the discovery of Sotorasib. This novel drug binds to a small pocket on the switch II of Kirsten rat sarcoma by exploiting the mutation that occurs at codon 12 wherein glycine is replaced by cysteine. However, this pocket is not only prone to cysteine mutation but other mutations occur as well including at codon 13. These mutations have been reported to drive cancer in the lungs, colorectal and in solid tumors with varying degree of expressions. Sotorasib is therefore only effective in a small group of patients especially those expressing cysteine at codon 12, reminding drug hunters of the unfinished work. This study employs computational techniques to understand the susceptibility of the mutated binding pocket to the binding of Sotorasib. It was revealed that the binding affinity of Sotorasib to other mutations aside Cysteine was significantly affected via the total free binding energies presented by the mutated complexes. Furthermore, the quantum of energy contributed by the mutated residues except cysteine was significantly reduced suggesting the binding of Sotorasib is enhanced in only cysteine mutated Kirsten rat sarcoma. Residual interaction network showed Sotorasib in complex with the cysteine mutated protein presented the highest degree centrality, shortest path betweenness, shortest path centrality and shortest path degree indicating Sotorasib controls more information flow within the cysteine mutated protein than in other mutations. Insight unraveled here will provide aid in the development of pan Kirsten rat sarcoma inhibitory small molecules.

DOCKING STUDIES OF THE MECHANISM OF ACTION OF A POTENTIAL NON-STEROIDAL ANTI-INFLAMMATORY AGENT 3-[(3,5-DICHLOROPYRIDIN-2-YL)OXY]- 3,4-DIHYDRO-2H-BENZO[4,5]-IMIDAZO[2,1-B][1,3]-THIAZINE

The work is devoted to the docking research of the mechanism of action of the nonsteroidal anti-inflammatory agent of the imidazothiazine type, 3-[(3,5-dichloropyridin-2-yl)oxy]-3,4-dihydro-2H-benzo[4,5]imidazo[2,1- b][1,3]-thiazine. The synthesized compound 4q with previously established high antioxidant activity was investigated for the docking of one molecule with another – molecular docking. According to the results of the experiment, it was established that the mechanism of anti-inflammatory activity of 4q is based on non-selective effect on cyclooxygenases of the first and second types. According to the docking simulation results, the presence of chlorine atom in the 4q molecule creates additional hydrophobic interaction that increases the total binding energy. As a result of the docking studies, it was found that 3-[(3,5-dichloropyridin-2-yl)oxy]-3,4-dihydro-2H-benzo[4,5] imidazo[2,1-b][ 1,3]-thiazine 4q when bound to COX-1 is placed in a hydrophobic pocket, the structure of which consists of a series of lipophilic amino acids, ILE563, VAL349, ALA527, LEU352, TRP387, PHE518, TYR385, TYR348, LEU 384. Additionally, 4q shows good binding to the active site of COX-2. This interaction is implemented due to hydrophobic interactions with a number of amino acids, VAL509, ALA513, VAL335, LEU370, TRP373 and TYR 371. Performed docking studies showed that 3-[(3,5-dichloropyridin-2-yl)oxy]-3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b] [1,3]-thiazine 4q forms a number of additional bonds with LEU338 (Pi-amide), ALA502 (Pi-alkyl), GLY512 (hydrogencarbon bond). However, similar to the binding to the COX-1 enzyme, the tested compound 4q did not form any hydrogen bonds. It was shown that 3-((3,5-dichloropyridin-2-yl)oxy)-3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]-thiazine 4q which demonstrated good binding to COX-1 and COX-2 enzymes in in silico docking studies even without the formation of hydrogen bonds can be used as an effective model scaffold for the design of new potential non-steroidal anti-inflammatory agents.

Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches.

Simple SummaryThe current study provides an insight into the binding and dynamic differences between wild-type RBD and B.1.620, which harbor S477N-E484K mutations in the spike protein’s receptor-binding domain (RBD). Our analysis revealed that though the number of hydrogen bonds and salt bridges remained the same, the binding affinity of B.1.620 for ACE2 was higher than that of the wild type, consequently increasing infectivity. Moreover, the stable dynamics and other features further justify the findings, corroborating the previous literature. Recently, a new variant, B.1620, with mutations (S477N-E484K) in the spike protein’s receptor-binding domain (RBD) has been reported in Europe. In order to design therapeutic strategies suitable for B.1.620, further studies are required. A detailed investigation of the structural features and variations caused by these substitutions, that is, a molecular level investigation, is essential to uncover the role of these changes. To determine whether and how the binding affinity of ACE2–RBD is affected, we used protein–protein docking and all-atom simulation approaches. Our analysis revealed that B.1.620 binds more strongly than the wild type and alters the hydrogen bonding network. The docking score for the wild type was reported to be −122.6 +/− 0.7 kcal/mol, while for B.1.620, the docking score was −124.9 +/− 3.8 kcal/mol. A comparative binding investigation showed that the wild-type complex has 11 hydrogen bonds and one salt bridge, while the B.1.620 complex has 14 hydrogen bonds and one salt bridge, among which most of the interactions are preserved between the wild type and B.1.620. A dynamic analysis of the two complexes revealed stable dynamics, which corroborated the global stability trend, compactness, and flexibility of the three essential loops, providing a better conformational optimization opportunity and binding. Furthermore, binding free energy revealed that the wild type had a total binding energy of −51.14 kcal/mol, while for B.1.628, the total binding energy was −68.25 kcal/mol. The current findings based on protein complex modeling and bio-simulation methods revealed the atomic features of the B.1.620 variant harboring S477N and E484K mutations in the RBD and the basis for infectivity. In conclusion, the current study presents distinguishing features of B.1.620, which can be used to design structure-based drugs against the B.1.620 variant.

Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment.

In the rural communities of sub-Saharan African (sSA) countries, malaria is being managed using phytocompounds. Artesunate is reported to inhibit Gephyrin E, a central, multi-domain scaffolding protein of inhibitory post-synapses. Neem plant and its metabolites like azadirachtin are being indicated for management of malaria by traditional healers. The present study was aimed to cheminformatically analyse the binding potential of artesunate and azadirachtin with various reactive moieties of Gephyrin E, to reduce malaria scourge. With molecular dynamics (MD), binding free energy estimation and binding affinity of artesunate and azadirachtin to Gephyrin E was done. GRIP docking was done to study the interactions of these test ligands with Gephyrin E (6FGC). MD simulation gave insights to structural changes upon binding of artesunate and azadirachtin in the ligand-binding pocket of Gephyrin E. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were calculated. From the estimation, azadirachtin had a total binding energy of −36.97 kcal/mol; artesunate had a binding energy of −35.73 kcal/mol. The GRIP docking results provided a clearer evidence that artesunate has comparatively better binding affinity to Gephyrin E than azadirachtin, and the critical binding sites (in activity order) were cavity 3, 2, 8, and 6 for artesunate while for azadirachtin, it was cavity 6, 3, 8, and 2. The GRIP docking provided detailed interactions at the atomic levels, providing evidence; both compounds have chances to overcome the drug resistance problem, albeit higher for artesunate. Our findings added another piece of evidence that azadirachtin may be effective as an anti-malarial agent. The results herein may provide impetus for more studies into bioactive components of plant origin towards the effective management of malaria disease phenotype.

R•-hole interactions of group IV-VII radical-containing molecules: A comparative study

For the first time, the potentiality of the sp2-hybridized group IV-VII radical (R•)-containing molecules to participate in R•-hole interactions was comparatively assessed using •SiF3,•POF2, •SO2F, and •ClO3 models in the trigonal pyramidal geometry. In that spirit, a plethora of quantum mechanical calculations was performed at the MP2/aug-cc-pVTZ level of theory. According to the results, all the investigated R•-containing molecules exhibited potent versatility to engage in R•-hole … Lewis base interactions with significant negative binding energies for the NCH-based complexes. The strength of R•-hole interactions was perceived to obey the •ClO3 … > •SO2F … > •POF2 … > •SiF3 … Lewis base order, outlining an inverse correlation between the binding energy and the atomic size of the R•-hole donor. Benchmarking of the binding energy at the CCSD/CBS(T) computational level was executed for all the explored interactions and addressed an obvious similarity between the MP2 and CCSD energetic findings. QTAIM analysis critically unveiled the closed-shell nature of the explored R•-hole interactions. SAPT-EDA proclaimed the reciprocal contributions of electrostatic and dispersion forces to the total binding energy. These observations demonstrate in better detail the nature of R•-hole interactions, leading to a convincing amelioration for versatile fields relevant to materials science and drug design.

Assessment of the van der Waals, Hubbard U parameter and spin-orbit coupling corrections on the 2D/3D structures from metal gold congeners clusters.

The coinage-metal clusters possess a natural complexity in their theoretical treatment that may be accompanied by inherent shortcomings in the methodological approach. Herein, we performed a scalar-relativistic density functional theory study, considering Perdew, Burke, and Ernzerhof (PBE) with (empirical and semi empirical) van der Waals (vdW), spin-orbit coupling (SOC), +U (Hubbard term), and their combinations, to treat the , , and clusters in different structural motifs. The energetic scenario is given by the confirmation of the 3D lowest energy configurations for and within all approaches, while for there is a 2D/3D competition, depending on the applied correction. The 2D geometry is 0.43 eV more stable with plain PBE than the 3D one, the SOC, +U, and/or vdW inclusion decreases the overestimated stability of the planar configurations, where the most surprising result is found by the D3 and D3BJ vdW corrections, for which the 3D configuration is 0.29 and 0.11 eV, respectively, more stable than the 2D geometry (with even higher values when SOC and/or +U are added). The D3 dispersion correction represents 7.9% (4.4%) of the total binding energy for the 3D (2D) configuration, (not) being enough to change the hybridization and the position of the occupied -states. Our predictions are in agreement with experimental results and in line with the best results obtained for bulk systems, as well as with hybrid functionals within D3 corrections. The properties description undergoes small corrections with the different approaches, where general trends are maintained, that is, the average bond length is smaller (larger) for lower (higher)-coordinated structures, since a same number of electrons are shared by a smaller (larger) number of bonds, consequently, the bonds are stronger (weaker) and shorter (longer) and the hybridization index is larger (smaller). Thus, Au has a distinct behavior in relation to its lighter congeners, with a complex potential energy surface, where in addition to the relevant relativistic effects, correlation and dispersion effects must also be considered.

Computational Evaluation of Abrogation of HBx-Bcl-xL Complex with High-Affinity Carbon Nanotubes (Fullerene) to Halt the Hepatitis B Virus Replication.

Hepatitis B virus (HBV) is the world’s most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target. Targeting the interface and discovering novel drugs greatly advanced the field of therapeutics development. Therefore, in the current study, HBx to Bcl-xL is abrogated on high-affinity carbon nanotubes using computational structural biology tools. Our analysis revealed that among the total 62 carbon fullerenes, only 13 compounds exhibited inhibitory activity against HBx, which was further confirmed through IFD-based rescoring. Structural dynamics investigation revealed stable binding, compactness, and hydrogen bonds reprogramming. Moreover, the binding free energy calculation results revealed that the top hits1-4 possess the total binding energy of −54.36 kcal/mol (hit1), −50.81 kcal/mol (hit2), −47.09 kcal/mol (hit3), and −45.59 kcal/mol for hit4. In addition, the predicted KD values and bioactivity scores further validated the inhibitory potential of these top hits. The identified compounds need further in vitro and in vivo validation to aid the treatment process of HBV.

Membrane-binding mechanism of the EEA1 FYVE domain revealed by multi-scale molecular dynamics simulations.

Early Endosomal Antigen 1 (EEA1) is a key protein in endosomal trafficking and is implicated in both autoimmune and neurological diseases. The C-terminal FYVE domain of EEA1 binds endosomal membranes, which contain phosphatidylinositol-3-phosphate (PI(3)P). Although it is known that FYVE binds PI(3)P specifically, it has not previously been described of how FYVE attaches and binds to endosomal membranes. In this study, we employed both coarse-grained (CG) and atomistic (AT) molecular dynamics (MD) simulations to determine how FYVE binds to PI(3)P-containing membranes. CG-MD showed that the dominant membrane binding mode resembles the crystal structure of EEA1 FYVE domain in complex with inositol-1,3-diphospate (PDB ID 1JOC). FYVE, which is a homodimer, binds the membrane via a hinge mechanism, where the C-terminus of one monomer first attaches to the membrane, followed by the C-terminus of the other monomer. The estimated total binding energy is ~70 kJ/mol, of which 50-60 kJ/mol stems from specific PI(3)P-interactions. By AT-MD, we could partition the binding mode into two types: (i) adhesion by electrostatic FYVE-PI(3)P interaction, and (ii) insertion of amphipathic loops. The AT simulations also demonstrated flexibility within the FYVE homodimer between the C-terminal heads and coiled-coil stem. This leads to a dynamic model whereby the 200 nm long coiled coil attached to the FYVE domain dimer can amplify local hinge-bending motions such that the Rab5-binding domain at the other end of the coiled coil can explore an area of 0.1 μm2 in the search for a second endosome with which to interact.

A rush to explore protein-ligand electrostatic interaction energy with Charger.

The mutual penetration of electron densities between two interacting molecules complicates the computation of an accurate electrostatic interaction energy based on a pseudo-atom representation of electron densities. The numerical exact potential and multipole moment (nEP/MM) method is time-consuming since it performs a 3D integration to obtain the electrostatic energy at short interaction distances. Nguyen et al. [(2018), Acta Cryst. A74, 524-536] recently reported a fully analytical computation of the electrostatic interaction energy (aEP/MM). This method performs much faster than nEP/MM (up to two orders of magnitude) and remains highly accurate. A new program library, Charger, contains an implementation of the aEP/MM method. Charger has been incorporated into the MoProViewer software. Benchmark tests on a series of small molecules containing only C, H, N and O atoms show the efficiency of Charger in terms of execution time and accuracy. Charger is also powerful in a study of electrostatic symbiosis between a protein and a ligand. It determines reliable protein-ligand interaction energies even when both contain S atoms. It easily estimates the individual contribution of every residue to the total protein-ligand electrostatic binding energy. Glutathione transferase (GST) in complex with a benzophenone ligand was studied due to the availability of both structural and thermodynamic data. The resulting analysis highlights not only the residues that stabilize the ligand but also those that hinder ligand binding from an electrostatic point of view. This offers new perspectives in the search for mutations to improve the interaction between the two partners. A proposed mutation would improve ligand binding to GST by removing an electrostatic obstacle, rather than by the traditional increase in the number of favourable contacts.

Unveiling the mechanistic roles of chlorine substituted phthalazinone-based compounds containing chlorophenyl moiety towards the differential inhibition of poly (ADP-ribose) polymerase-1 in the treatment of lung cancer

PARP-1 has become an attractive target in cancer treatment owing to its significant role in breast and ovarian cancers. The design of highly selective and effective poly (ADP ribose) polymerase-1 inhibitors has significant therapeutic advantages and has remained the core of several PARP-1-based drug discovery research. The pharmacophoric relevance of a chlorine substituent in a recent study led to the design of compounds 11c (meta-chlorophenyl) and 11d (para-chlorophenyl). In this study, we resolved the mechanistic effects of the changes in chlorine positional orientation, which underlie the inhibitory potencies and selectivity exhibited disparately by 11c and 11d. Compared to 11d, among other multiple higher-affinity complementary interactions with key site residues, the meta-Cl positioning in 11c facilitated its optimal motion and orientation towards conserved residues Arg878 and Asp766 with consistent pi-cation and pi-anion interactions, respectively, thereby favoring the stability of the ligand towards PARP-1. These could account for the higher inhibitory potency exhibited by 11c relative to 11d against PARP-1. The thermodynamics calculation revealed that 11c had a relatively higher total binding energy (ΔGbind) than 11d. We also observed that 11d displayed high deviations, compared to 11c, indicative of its unstable binding orientation. Furthermore, we reported in this study that the high involvement of electrostatic and van der Waal effects potentiated the binding affinity and strength of 11c (ΔEvdW = −50.58 and ΔEele = −27.20) relative to 11d (ΔEvdW = −49.46 and ΔEele = −19.96) at PARP-1 binding pocket. We believe the findings in this current study would provide valuable insights into the design of selective PARP-1 inhibitors containing chlorine substituent for cancer treatment, including lung cancer. Communicated by Ramaswamy H. Sarma

Drug repurposing approach against Mycobacterium tuberculosis Enoyl-[acyl-carrier-protein] reductase: insight from molecular dynamics simulations

ABSTRACT Enoyl-[acyl-carrier-protein] reductase (InhA) is one of the major targets for the inhibition of Mycobacterium tuberculosis (Mtb). Herein, we introduce a drug repurposing approach against Mtb-InhA: Insight from molecular dynamic simulations. The approach was found hopeful to identify in silico hits with better binding affinities as compared to isoniazid. Four drug hits displayed higher total binding energies (ΔG tot) in relation to isoniazid with DB04007 exhibiting the highest ΔG tot of −41.11 kcal/mol as compared to the −7.89 kcal/mol from isoniazid. Herein, the results revealed that the isoniazid is less stable compared to DB04007. Hence, this pattern was reiterated by the lower RoG of DB04007. Both DB04007 and isoniazid exhibited a structural evolution denoted to common flexibility changes. A distinct increase in fluctuation was seen in the RMSF of DB04007 which could be attributed to Ser92 forming 2 hydrogen bonds with the inhibitor, the distal amino acids affecting stability and the evolution of residues 195-210 from a primary to a secondary structure. DB04007 exhibited a higher total binding free energy due to the residual van der Waals and hydrogen bonding interactions as compared to the isoniazid. This approach can potentially serve as a platform for the development and discovery of novel drugs.

A universal relationship between stellar masses and binding energies of galaxies

ABSTRACT In this study, we demonstrate that stellar masses of galaxies (Mstar) are universally correlated through a double power-law function with the product of the dynamical velocities (Ve) and sizes to one-fourth power ($R_{\rm e}^{0.25}$) of galaxies, both measured at the effective radii. The product $V_{\rm e}R_{\rm e}^{0.25}$ represents the fourth root of the total binding energies within effective radii of galaxies. This stellar mass-binding energy correlation has an observed scatter of 0.14 dex in log($V_{\rm e}R_{\rm e}^{0.25}$) and 0.46 dex in log(Mstar). It holds for a variety of galaxy types over a stellar mass range of nine orders of magnitude, with little evolution over cosmic time. A toy model of self-regulation between binding energies and supernovae feedback is shown to be able to reproduce the observed slopes, but the underlying physical mechanisms are still unclear. The correlation can be a potential distance estimator with an uncertainty of 0.2 dex independent of the galaxy type.

Molecular docking, drug likeliness and in silico ADMET study of bioactive compounds against DNA methyltransferase

There is no proper cure for cancer even after so many years and with every progressing year as the drugs are getting more resistant and toxic, chances for recovering from cancer reduces. This present work represents the potential role of active natural metabolites present in common spices as proposed anticancer molecule. We report molecular docking of ferulic acid, crocetin, cinamaldehyde, fernesol and alpha tumerone against cancer target enzyme, DNA methyl transferase to determine their strong binding affinity, studied various others in silico properties like the drug likeliness behavior and absorption, distribution, metabolism, elimination and toxicity (ADMET) behavior. Our preliminary study reveals that all the five natural metabolites have the potential to behave like drugs, follows Lipinski’s rule of 5 and are non-carcinogenic. These bioactive compounds shows better solubility, good absorption and permeability and are non-toxic to mammalian cell Molecular docking shows crocetin and alpha tumerone to be a good inhibitor for DNA methyl transferase with a high total binding energy of −44.84 K cal/mol and −41.44 Kcal/mol respectively. Asn 779, Gln 188, Glu 303, Tyr 681, His 677, Glu 593 and Arg 840 of the target enzyme are involved in the hydrogen bond formation with all the five compounds. Our initial finding concludes that all the five bioactive compounds have the potential for proposing them as anticancer drugs.

A Quantum Chemical Topology Picture of Intermolecular Electrostatic Interactions and Charge Penetration Energy.

Based on the Interacting Quantum Atoms approach, we present herein a conceptual and theoretical framework of short-range electrostatic interactions, whose accurate description is still a challenging problem in molecular modeling. For all the noncovalent complexes in the S66 database, the fragment-based and atomic decomposition of the electrostatic binding energies is performed using both the charge density of the dimers and the unrelaxed densities of the monomers. This energy decomposition together with dispersion corrections gives rise to a pairwise approximation to the total binding energy. It also provides energetic descriptors at varying distance that directly address the atomic and molecular electrostatic interactions as described by point-charge or multipole-based potentials. Additionally, we propose a consistent definition of the charge penetration energy within quantum chemical topology, which is mainly characterized in terms of the intramolecular electrostatic energy. Finally, we discuss some practical implications of our results for the design and validation of electrostatic potentials.

Adsorption properties of amino acid-based ionic liquids (AAILs) on edge fluorinated graphene surface – a DFT study

ABSTRACT We have investigated the adsorption properties of amino acid-based ionic liquids (AAILs) on edge fluorinated graphene surface (FG). Adsorption of organic ILs on the FG surface occurs via hydrogen bonds (X-H···FC), electrostatic interactions, and π···π interactions. There are large charge transfers between the interfaces, primarily from the lone pair of the fluorine (C-F bond) to the X-H (X = C, N, O) bond of both cations/anions AAILs. These non-conventional reversible hydrogen bridges are essential in surface interactions. However, substantial charge transfer occurs to cations and anions in both aromatic and aliphatic systems, respectively. Interestingly, aromatic AAILs are firmly physisorbed than aliphatic ILs. The inclusion of dispersion corrections increases the accuracy of total binding energy contributions from multiple adsorption interactions and predicts the complex's kinetic stability. Molar volume values determine the materiality of AAIL/FG to bulk systems.

Structural and Biophysical Investigation of the Key Hotspots on the Surface of Epstein-Barr Nuclear Antigen 1 Essential for DNA Recognition and Pathogenesis.

Epstein-Barr Virus (EBV) is considered the most important human pathogen due to its role in infections and cellular malignancies. It has been reported that this Oncolytic virus infects 90% world’s population. EBNA1 is required for DNA binding and survival of the virus and is considered an essential drug target. The biochemical and structural properties of this protein are known, but it is still unclear which residues impart a critical role in the recognition of dsDNA. Intending to disclose only the essential residues in recognition of dsDNA, this study used a computational pipeline to generate an alanine mutant of each interacting residue and determine the impact on the binding. Our analysis revealed that R469A, K514A, Y518A, R521A and R522A are the key hotspots for the recognition of dsDNA by the EBNA1. The dynamics properties, i.e. stability, flexibility, structural compactness, hydrogen bonding frequency, binding affinity, are altered by disrupting the protein-DNA contacts, thereby decreases the binding affinity. In particular, the two arginine substitution, R521A and R522A, significantly affected the total binding energy. Thus, we hypothesize that these residues impart a critical role in the dsDNA recognition and pathogenesis. This study would help to design structure-based drugs against the EBV infections.

Exploring the inhibitory potentials of Momordica charantia bioactive compounds against Keap1-Kelch protein using computational approaches.

The online version contains supplementary material available at 10.1007/s40203-021-00100-2.

Interactions and Binding Energies in Carbon Nanotube Bundles

On any size scale, it is important to know how strongly structural components are held together. The purpose of this work was to develop a means to estimate the collective binding energy holding together a bundle of aligned carbon nanotubes (CNTs). Carbon nanotubes in isolation and in bundles have unique and useful properties and applications within supramolecular structures and nanotechnology. Equations were derived to represent the total number of pairwise interactions between the CNTs found in various size and shape bundles. The shapes considered included diamond, hexagon, parallelogram, and rectangle. Parameters were used to characterize the size of a bundle for each defined shape. Force field molecular modeling was used to obtain the total bundle binding energies for a number of sample bundles. From the number of interactions per bundle, the binding energy per interaction was determined. This process was repeated for armchair CNTs having a range of length and circumference values. A simple equation described the interaction energy based on the length and circumference of the component armchair type nanotubes. When combined with the bundle shape and size parameters, the total bundle binding energy could be found. Comparison with whole bundle molecular mechanics calculations showed our formula-based approach to be effective.

Relativistic effective charge model of a multi-electron atom

A relativistic version of the effective charge model (ECM) for computation of observable characteristics of multi-electron atoms and ions is developed. A complete and orthogonal Dirac hydrogen basis set, depending on one parameter—effective nuclear charge Z*—identical for all single-electron wave functions of a given atom or ion, is employed for the construction of the secondary-quantized representation. The effective charge is uniquely determined by the charge of the nucleus and a set of occupied single-electron orbitals for a given state. We thoroughly study the accuracy of the leading-order approximation for the total binding energy and demonstrate that it is independent of the number of electrons of a multi-electron atom. In addition, it is shown that the fully analytical leading-order approximation is especially suited for the description of highly charged ions since our wave functions are almost coincident with the Dirac–Hartree–Fock ones for the complete spectrum. Finally, we evaluate various atomic characteristics, such as scattering factors and photoionization cross-sections, and thus envisage that the ECM can replace other models of comparable complexity, such as the Thomas–Fermi–Dirac model for all applications where it is still utilized.