Drug and Drug-like Molecule Binding to Interface of SARS-CoV-2 Sprotein:human ACE2 Complex: A Density Functional Theory Study

10.26434/chemrxiv.13066061.v1 ◽

2020 ◽

Author(s):

CH Suresh

Keyword(s):

Binding Energy ◽

Density Functional ◽

Rational Design ◽

Noncovalent Interactions ◽

Receptor Interaction ◽

Site Model ◽

Model Drug ◽

Drug Receptor ◽

Approved Drugs ◽

Better Than

SARS-CoV-2 S-protein:human ACE2 complex models.<div>QM-MM optimized active site model of SARS-CoV-2 S-protein:human ACE2 interface.</div><div>ONIOM(B3LYP/6-31G*:PM7) method is the chosen QM-MM method. </div><div> DFT B3LYP/6-31G* level data on energetics is reported for drug-receptor interaction.</div><div>Several FDA approved drugs and traditional herbal isolates are modelled.</div><div>Used Gaussian16 to model the systems.</div><div><br></div><div><br></div><p>The interface cavity of SARS-CoV-2 S-protein:human ACE2 complex (<b>M</b>) for ligand (<b>L</b>) binding is modelled using a two layer ONIOM(B3LYP/6-31G*:PM7) method for sixteen traditional herbal isolates (THI) and nineteen drugs. The binding energy (E<sub>b</sub>) of <b>ML</b> complexes increased with increase in dipole moment of <b>L</b>s. E<sub>b</sub> better than -80.0 kcal/mol is observed for digallic acid and adenosine 3',5'-bisphosphate whereas myricetin, glucogallin, sapropterin, tetrahydrobiopterin, protirelin and fidarestat<b> </b>showed E<sub>b</sub> better than -60.0 kcal/mol. Multiple noncovalent interactions emanating from arginine, histidine, tyrosine, lysine, carboxylate and amide units (total around 6 - 8) of <b>L</b>, S-protein and ACE2 receptors provide the high binding energy. The sugar substitute aspartame modified with myricetin unit showed the best E<sub>b</sub> -91.7 kcal/mol. ONIOM-linked DFT study is effective, affordable and reliable for a quantum chemical rational design approach to model drug-receptor binding process for COVID-19 drug development which sheds light upon the noncovalent binding features of receptor cavity.</p>

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Noncovalent Interactions of 1,4-Dithiafulvene and Nitroaromatics: A Combined DFT and Ab Initio Molecular Dynamics (AIMD) Study

10.22541/au.163836337.74662602/v1 ◽

2021 ◽

Author(s):

Yuming Zhao ◽

Cody Marcus King-Poole

Keyword(s):

Molecular Dynamics ◽

Ab Initio ◽

Density Functional ◽

Rational Design ◽

Environmental Control ◽

Noncovalent Interactions ◽

Picric Acid ◽

Decomposition Analysis ◽

Ab Initio Molecular Dynamics ◽

Energy Decomposition Analysis

The noncovalent interactions between a redox-active molecule, phenyl-substituted dithiafulvene (Ph-DTF), and ten commonly encountered nitroaromatic compounds (NACs) were systematically investigated by means of density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations. Our modeling studies examined their 1:1 complexes in terms of equilibrium geometries, frontier molecular orbitals (FMOs), nature of noncovalent forces, intermolecular charge transfer (ICT), interaction energies and related energy decomposition analysis. The computational results indicate that Ph-DTF can form thermodynamically stable supramolecular complexes with trinitro-substituted benzenes (e.g., 2,4,6-trinisuchtrotoluene and picric acid), but its interactions with mono- and dinitrobenzenes do not exhibit such stability. The selective binding properties are further corroborated by AIMD simulations. Overall, this computational work establishes a comprehensive understanding of the nature of noncovalent interactions of Ph-DTF with various NACs, and the results can be used as theoretical guidance for the rational design of selective receptors and/or chemosensors for certain NACs that are of great concern in current industrial applications and environmental control.

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High-Entropy Alloys as Catalysts for the CO2 and CO Reduction Reactions

10.26434/chemrxiv.9850997.v1 ◽

2019 ◽

Author(s):

Jack Pedersen ◽

Thomas Batchelor ◽

Alexander Bagger ◽

Jan Rossmeisl

Keyword(s):

Density Functional ◽

Rational Design ◽

Hydrogen Adsorption ◽

Co Adsorption ◽

Reduction Reaction ◽

Supervised Machine Learning ◽

High Entropy Alloys ◽

High Entropy ◽

Co Reduction ◽

Disordered Alloy

Using the high-entropy alloys (HEAs) CoCuGaNiZn and AgAuCuPdPt as starting points we provide a framework for tuning the composition of disordered multi-metallic alloys to control the selectivity and activity of the reduction of carbon dioxide (CO2) to highly reduced compounds. By combining density functional theory (DFT) with supervised machine learning we predicted the CO and hydrogen (H) adsorption energies of all surface sites on the (111) surface of the two HEAs. This allowed an optimization for the HEA compositions with increased likelihood for sites with weak hydrogen adsorption{to suppress the formation of molecular hydrogen (H2) and with strong CO adsorption to favor the reduction of CO. This led to the discovery of several disordered alloy catalyst candidates for which selectivity towards highly reduced carbon compounds is expected, as well as insights into the rational design of disordered alloy catalysts for the CO2 and CO reduction reaction.

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A DFT study of spherands containing five anisyl groups — Highly preorganized to bind the alkali metal

Canadian Journal of Chemistry ◽

10.1139/v06-130 ◽

2006 ◽

Vol 84 (8) ◽

pp. 1045-1049 ◽

Cited By ~ 4

Author(s):

Shabaan AK Elroby ◽

Kyu Hwan Lee ◽

Seung Joo Cho ◽

Alan Hinchliffe

Keyword(s):

Density Functional Theory ◽

Binding Energy ◽

Density Functional ◽

Ionic Radius ◽

Binding Energies ◽

Cavity Size ◽

X Ray Diffraction ◽

Functional Theory ◽

X Ray ◽

Good Agreement

Although anisyl units are basically poor ligands for metal ions, the rigid placements of their oxygens during synthesis rather than during complexation are undoubtedly responsible for the enhanced binding and selectivity of the spherand. We used standard B3LYP/6-31G** (5d) density functional theory (DFT) to investigate the complexation between spherands containing five anisyl groups, with CH2–O–CH2 (2) and CH2–S–CH2 (3) units in an 18-membered macrocyclic ring, and the cationic guests (Li+, Na+, and K+). Our geometric structure results for spherands 1, 2, and 3 are in good agreement with the previously reported X-ray diffraction data. The absolute values of the binding energy of all the spherands are inversely proportional to the ionic radius of the guests. The results, taken as a whole, show that replacement of one anisyl group by CH2–O–CH2 (2) and CH2–S–CH2 (3) makes the cavity bigger and less preorganized. In addition, both the binding and specificity decrease for small ions. The spherands 2 and 3 appear beautifully preorganized to bind all guests, so it is not surprising that their binding energies are close to the parent spherand 1. Interestingly, there is a clear linear relation between the radius of the cavity and the binding energy (R2 = 0.999).Key words: spherands, preorganization, density functional theory, binding energy, cavity size.

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Specific inhibition of the Survivin–CRM1 interaction by peptide-modified molecular tweezers

Nature Communications ◽

10.1038/s41467-021-21753-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Annika Meiners ◽

Sandra Bäcker ◽

Inesa Hadrović ◽

Christian Heid ◽

Christine Beuck ◽

...

Keyword(s):

Nuclear Export ◽

Rational Design ◽

Nuclear Export Signal ◽

Signal Interference ◽

Receptor Interaction ◽

Dual Function ◽

Experimental Proof ◽

Molecular Tweezers ◽

Recognition Element ◽

Dynamics Simulations

AbstractSurvivin’s dual function as apoptosis inhibitor and regulator of cell proliferation is mediated via its interaction with the export receptor CRM1. This protein–protein interaction represents an attractive target in cancer research and therapy. Here, we report a sophisticated strategy addressing Survivin’s nuclear export signal (NES), the binding site of CRM1, with advanced supramolecular tweezers for lysine and arginine. These were covalently connected to small peptides resembling the natural, self-complementary dimer interface which largely overlaps with the NES. Several biochemical methods demonstrated sequence-selective NES recognition and interference with the critical receptor interaction. These data were strongly supported by molecular dynamics simulations and multiscale computational studies. Rational design of lysine tweezers equipped with a peptidic recognition element thus allowed to address a previously unapproachable protein surface area. As an experimental proof-of-principle for specific transport signal interference, this concept should be transferable to any protein epitope with a flanking well-accessible lysine.

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A theoretical and experimental study of the adsorptive removal of hexavalent chromium ions using graphene oxide as an adsorbent

Open Chemistry ◽

10.1515/chem-2020-0148 ◽

2020 ◽

Vol 18 (1) ◽

pp. 936-942

Author(s):

Ardhmeri Alija ◽

Drinisa Gashi ◽

Rilinda Plakaj ◽

Admir Omaj ◽

Veprim Thaçi ◽

...

Keyword(s):

Graphene Oxide ◽

Hexavalent Chromium ◽

Adsorption Energy ◽

Density Functional ◽

Noncovalent Interactions ◽

Theoretical Calculations ◽

Chemical Oxidation ◽

Chromium Ions ◽

Adsorption Sites ◽

Vis Spectroscopy

AbstractThis study is focused on the adsorption of hexavalent chromium ions Cr(vi) using graphene oxide (GO). The GO was prepared by chemical oxidation (Hummers method) of graphite particles. The synthesized GO adsorbent was characterized by Fourier transform infrared spectroscopy and UV-Vis spectroscopy. It was used for the adsorption of Cr(vi) ions. The theoretical calculations based on density functional theory and Monte Carlo calculations were used to explore the preferable adsorption site, interaction type, and adsorption energy of GO toward the Cr(vi) ions. Moreover, the most stable adsorption sites were used to calculate and plot noncovalent interactions. The obtained results are important as they give molecular insights regarding the nature of the interaction between GO surface and the adsorbent Cr(vi) ions. The found adsorption energy of −143.80 kcal/mol is indicative of the high adsorptive tendency of this material. The adsorption capacity value of GO toward these ions is q = 240.361 mg/g.

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Engineering single-atomic ruthenium catalytic sites on defective nickel-iron layered double hydroxide for overall water splitting

Nature Communications ◽

10.1038/s41467-021-24828-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Panlong Zhai ◽

Mingyue Xia ◽

Yunzhen Wu ◽

Guanghui Zhang ◽

Junfeng Gao ◽

...

Keyword(s):

Hydrogen Evolution ◽

Water Splitting ◽

Layered Double Hydroxide ◽

Hydrogen Evolution Reaction ◽

Active Sites ◽

Density Functional ◽

Rational Design ◽

Single Atom ◽

Nickel Iron ◽

Double Hydroxide

AbstractRational design of single atom catalyst is critical for efficient sustainable energy conversion. However, the atomic-level control of active sites is essential for electrocatalytic materials in alkaline electrolyte. Moreover, well-defined surface structures lead to in-depth understanding of catalytic mechanisms. Herein, we report a single-atomic-site ruthenium stabilized on defective nickel-iron layered double hydroxide nanosheets (Ru1/D-NiFe LDH). Under precise regulation of local coordination environments of catalytically active sites and the existence of the defects, Ru1/D-NiFe LDH delivers an ultralow overpotential of 18 mV at 10 mA cm−2 for hydrogen evolution reaction, surpassing the commercial Pt/C catalyst. Density functional theory calculations reveal that Ru1/D-NiFe LDH optimizes the adsorption energies of intermediates for hydrogen evolution reaction and promotes the O–O coupling at a Ru–O active site for oxygen evolution reaction. The Ru1/D-NiFe LDH as an ideal model reveals superior water splitting performance with potential for the development of promising water-alkali electrocatalysts.

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