scholarly journals Multiscale modeling of bio-nano interactions of zero-valent silver nanoparticles.

2021 ◽  
Author(s):  
Julia Subbotina ◽  
Vladimir Lobaskin
Keyword(s):  
Silver Nanoparticles ◽  
High Throughput Screening ◽  
Computational Study ◽  
Bovine Lactoferrin ◽  
Multiscale Approach ◽  
Binding Affinities ◽  
Serum Albumins ◽  
Drug Molecules ◽  
Protein Libraries ◽  
Starting Model

Understanding the specifics of interaction between protein and nanomaterial is crucial for designing efficient, safe, and selective nanoplatforms, such as biosensor or nanocarrier systems. Routing experimental screening for the most suitable complementary pair of biomolecule and nanomaterial used in such nanoplatforms might be a resource-intensive task. While a variety of computational tools is available for pre-screening libraries of small drug molecules interacting with proteins, options for high-throughput screening of protein libraries for binding affinities to new and existing nanomaterials are limited. In the current work, we present the results of a systematic computational study of protein interaction with zero-valent silver nanoparticles using a multiscale approach. A variety of blood plasma and dietary proteins, namely, bovine and human serum albumins, bovine and human hemoglobin, papain, bromelain, lysozyme, and bovine lactoferrin, were examined. Selected combinations of nanomaterial and proteins can serve as a starting model for developing noble metal-based nanocarriers and biosensors. The computed binding (adsorption) characteristics for selected proteins were validated by experimental data reported in the literature. An advanced in silico nano-QSAR/QSPR interfacial descriptor 〖log⁡P〗^NM was also introduced to characterize the relative hydrophobicity/hydrophilicity of the nanomaterial.

Accelerated Discovery of High-Refractive-Index Polyimides via First-Principles Molecular Modeling, Virtual High-Throughput Screening, and Data Mining

2019 ◽  
Author(s):  
Mohammad Atif Faiz Afzal ◽  
Mojtaba Haghighatlari ◽  
Sai Prasad Ganesh ◽  
Chong Cheng ◽  
Johannes Hachmann
Keyword(s):  
Data Mining ◽  
Refractive Index ◽  
High Throughput ◽  
First Principles ◽  
High Throughput Screening ◽  
Large Scale ◽  
Computational Study ◽  
High Refractive Index ◽  
Structural Features ◽  
Learning Program

<div>We present a high-throughput computational study to identify novel polyimides (PIs) with exceptional refractive index (RI) values for use as optic or optoelectronic materials. Our study utilizes an RI prediction protocol based on a combination of first-principles and data modeling developed in previous work, which we employ on a large-scale PI candidate library generated with the ChemLG code. We deploy the virtual screening software ChemHTPS to automate the assessment of this extensive pool of PI structures in order to determine the performance potential of each candidate. This rapid and efficient approach yields a number of highly promising leads compounds. Using the data mining and machine learning program package ChemML, we analyze the top candidates with respect to prevalent structural features and feature combinations that distinguish them from less promising ones. In particular, we explore the utility of various strategies that introduce highly polarizable moieties into the PI backbone to increase its RI yield. The derived insights provide a foundation for rational and targeted design that goes beyond traditional trial-and-error searches.</div>

scholarly journals Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6821
Author(s):  
Rasel Ahmed Khan ◽  
Rajib Hossain ◽  
Abolghasem Siyadatpanah ◽  
Khattab Al-Khafaji ◽  
Abul Bashar Ripon Khalipha ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Computational Study ◽  
Viral Proteins ◽  
Network Pharmacology ◽  
Binding Affinities ◽  
Ns1 Protein ◽  
Structural Protein ◽  
E Protein

Dengue fever is a dangerous infectious endemic disease that affects over 100 nations worldwide, from Africa to the Western Pacific, and is caused by the dengue virus, which is transmitted to humans by an insect bite of Aedes aegypti. Millions of citizens have died as a result of dengue fever and dengue hemorrhagic fever across the globe. Envelope (E), serine protease (NS3), RNA-directed RNA polymerase (NS5), and non-structural protein 1 (NS1) are mostly required for cell proliferation and survival. Some of the diterpenoids and their derivatives produced by nature possess anti-dengue viral properties. The goal of the computational study was to scrutinize the effectiveness of diterpenoids and their derivatives against dengue viral proteins through in silico study. Methods: molecular docking was performed to analyze the binding affinity of compounds against four viral proteins: the envelope (E) protein, the NS1 protein, the NS3 protein, and the NS5 protein. Results: among the selected drug candidates, triptolide, stevioside, alepterolic acid, sphaeropsidin A, methyl dodovisate A, andrographolide, caesalacetal, and pyrimethamine have demonstrated moderate to good binding affinities (−8.0 to −9.4 kcal/mol) toward the selected proteins: E protein, NS3, NS5, and NS1 whereas pyrimethamine exerts −7.5, −6.3, −7.8, and −6.6 kcal/mol with viral proteins, respectively. Interestingly, the binding affinities of these lead compounds were better than those of an FDA-approved anti-viral medication (pyrimethamine), which is underused in dengue fever. Conclusion: we can conclude that diterpenoids can be considered as a possible anti-dengue medication option. However, in vivo investigation is recommended to back up the conclusions of this study.

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

A Novel Green Biogenic Synthesis of Silver Nanoparticles using Tabebuia rosea (Bertol.) DC Fruit Extract and Its Antioxidant and Antibacterial Potential

2021 ◽  
Vol 14 (1) ◽  
pp. 5323-5333
Author(s):  
Dr. Guru Kumar Dugganaboyana ◽  
Ramya Jayendra ◽  
Arpitha Narayan ◽  
Meghana Siddappa Konasur
Keyword(s):  
Silver Nanoparticles ◽  
Diffusion Method ◽  
Phytochemical Analysis ◽  
Fruit Extract ◽  
Synthesis Of Nanoparticles ◽  
Drug Molecules ◽  
Agar Disc ◽  
Tabebuia Rosea ◽  
Average Size ◽  
Antibacterial Potential

Plant based synthesis of nanoparticles has generated worldwide interest because of cost-effectiveness, eco-friendly nature and abundance of applications. In the present investigation , antimicrobial potential of silver nanoparticles (AgNPs) of aqueous extract of Tabebuia rosea (Bertol.) DC (T. rosea) fruit extract has been investigated. Agar disc diffusion method was used for determining the antimicrobial activity of selected aqueous fruit extract AgNPs. Phytochemical analysis of aqueous fruit extract of T. rosea fruit revealed the presence of alkaloids, flavonoids, tannins, phenols, carbohydrates, glycosides, Vitamin-C, proteins and terpenoids. AgNPs synthesis using T. rosea aqueous fruit extract and characterized by UV-Visible spectroscopy showed a peak at 420 nm and average size of 82.9 nm, FT-IR analysis, dynamic light scattering, scanning electron microscope, EDX and X-ray diffraction analysis. Evaluation of antibacterial activity of green synthesized AgNPs recorded the more potent activity against selected human bacterial pathogens. The results obtained indicated that the fruit extract of T. rosea as well as AgNPs have strong and effective antibacterial potential that provide marvelous source for the development of new drug molecules of herbal origin which may be used for the welfare of humanity.

scholarly journals Computational Study of the Interaction of a PEGylated Hyperbranched Polymer/Doxorubicin Complex with a Bilipid Membrane

Fluids ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 17 ◽  
Author(s):  
Prodromos Arsenidis ◽  
Kostas Karatasos
Keyword(s):  
Hyperbranched Polymer ◽  
Lipid Membrane ◽  
Hydrophobic Interactions ◽  
Computational Study ◽  
Translational Motion ◽  
Spatial Arrangement ◽  
Aqueous Environment ◽  
Drug Molecules ◽  
Dynamics Simulations ◽  
A Charge

Fully atomistic molecular dynamics simulations are employed to study in detail the interactions between a complex comprised by a PEGylated hyperbranched polyester (HBP) and doxorubicin molecules, with a model dipalmitoylphosphatidylglycerol membrane in an aqueous environment. The effects of the presence of the lipid membrane in the drug molecules’ spatial arrangement were examined in detail and the nature of their interaction with the latter were discussed and quantified where possible. It was found that a partial migration of the drug molecules towards the membrane’s surface takes place, driven either by hydrogen-bonding (for the protonated drugs) or by hydrophobic interactions (for the neutral drug molecules). The clustering behavior of the drug molecules appeared to be enhanced in the presence of the membrane, while the development of a charge excess close to the surface of the hyperbranched polymer and of the lipid membrane was observed. The uneven charge distribution created an effective overcharging of the HBP/drug complex and the membrane/drug surface. The translational motion of the drug molecules was found to be strongly affected by the presence of the membrane. The extent of the observed changes depended on the charge of the drug molecule. The build-up of the observed charge excesses close to the surface of the polymeric host and the membrane, together with the changes in the diffusional behavior of the drug molecules are of particular interest. Both phenomena could be important at the latest stages of the liposomal disruption and the release of the drug cargo in formulations based on relevant liposomal carriers.

scholarly journals Computational study of fluorescence scattering by silver nanoparticles

2007 ◽  
Vol 24 (9) ◽  
pp. 2259 ◽  
Author(s):  
Mustafa H. Chowdhury ◽  
Stephen K. Gray ◽  
James Pond ◽  
Chris D. Geddes ◽  
Kadir Aslan ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Computational Study

scholarly journals Current Trends in SPR Biosensing of SARS-CoV-2 Entry Inhibitors

Chemosensors ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 330
Author(s):  
Elba Mauriz ◽  
Laura M. Lechuga
Keyword(s):  
High Throughput Screening ◽  
Antiviral Agents ◽  
Host Cells ◽  
Binding Affinities ◽  
Entry Inhibitors ◽  
Antiviral Compounds ◽  
Current Trends ◽  
Main Protease ◽  
Emerging Risk ◽  
Repurposed Drugs

The emerging risk of viral diseases has triggered the search for preventive and therapeutic agents. Since the beginning of the COVID-19 pandemic, greater efforts have been devoted to investigating virus entry mechanisms into host cells. The feasibility of plasmonic sensing technologies for screening interactions of small molecules in real time, while providing the pharmacokinetic drug profiling of potential antiviral compounds, offers an advantageous approach over other biophysical methods. This review summarizes recent advancements in the drug discovery process of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) inhibitors using Surface Plasmon Resonance (SPR) biosensors. A variety of SPR assay formats are discussed according to the binding kinetics and drug efficacies of both natural products and repurposed drugs. Special attention has been given to the targeting of antiviral agents that block the receptor binding domain of the spike protein (RBD-S) and the main protease (3CLpro) of SARS-CoV-2. The functionality of plasmonic biosensors for high-throughput screening of entry virus inhibitors was also reviewed taking into account experimental parameters (binding affinities, selectivity, stability), potential limitations and future applications.

scholarly journals A Mega-High-Throughput Screening Platform for the Discovery of Biologically Relevant Sequence-Defined Non-Natural Polymers

2020 ◽  
Author(s):  
Michal Avital-Shmilovici ◽  
Xiaohe Liu ◽  
Thomas Shaler ◽  
Andrew Lowenthal ◽  
Pauline Bourbon ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Binding Affinities ◽  
Natural Polymers ◽  
Protein Targets ◽  
Biologically Relevant ◽  
Novel Technology ◽  
Major Bottleneck ◽  
Screening Platform ◽  
Optic Array

Combinatorial methods enable the synthesis of chemical libraries on scales of millions to billions of compounds, but the ability to efficiently screen and sequence such large libraries has remained a major bottleneck for molecular discovery. We developed a novel technology for screening and sequencing libraries of synthetic molecules of up to a billion compounds in size. This method utilizes Fiber-optic Array Scanning Technology (FAST) to screen bead-based libraries of synthetic compounds at a rate of 5 million compounds per minute (~83,000 Hz). This ultra-high-throughput screening platform has been used to screen libraries of synthetic “self-readable” non-natural polymers that can be sequenced at femtomole scale by chemical fragmentation and highresolution mass spectrometry. The versatility and throughput of the platform was demonstrated by screening two libraries of non-natural polyamide polymers with sizes of 1.77M and 1B compounds against the protein targets K-Ras, asialoglycoprotein receptor (ASGPR), IL-6, IL-6 receptor and TNFα. Hits with nanomolar binding affinities were found against all targets, including competitive inhibitors of K-Ras binding to Raf and functionally active uptake ligands for ASGPR facilitating intracellular delivery.

A Computational Study to Prevent HIV Invasion by Bovine LF in Mucosal-Layer via Blocking of DC-SIGN_GP120 Interaction

2020 ◽  
Vol 17 (5) ◽  
pp. 413-424
Author(s):  
Arundhati Banerjee ◽  
Rakhi Dasgupta ◽  
Sujay Ray
Keyword(s):  
Computational Study ◽  
Sexual Transmission ◽  
Pharmaceutical Research ◽  
Active Role ◽  
Binding Pocket ◽  
Protein Docking ◽  
Bovine Lactoferrin ◽  
Stability Parameters ◽  
Mucosal Layer ◽  
Mucosal Lining

Background: Invasion of HIV in human occurs through DC-SIGN’s interaction via the mucosal lining during sexual transmission. Bovine Lactoferrin (bLF) has been known to hinder this invasion via its interaction with DC-SIGN. Hitherto, protein assays have taken place but molecular-level studies remain unexplored. Methodology: The 3D structures of the three proteins were studied. After protein docking (bLF_DCSIGN and gp120_DC-SIGN), the complexes underwent simulation. Stability parameters and binding patterns with residues were explored. Results and Conclusion: ΔG values, net area for solvent accessibilities and conformational fluctuations in DC-SIGN affirm the binding of bLF with DC-SIGN to be more spontaneous and steadier contrary to that with gp120. Residue participation inferred more interactions to occur from bLF complex with a greater percentage of arginine (which strengthens the interaction) while electrostatic interaction between Lys45 (bLF) and Glu26 (DC-SIGN) strengthened the complex. Arg37 played an active role from DC-SIGN to form the stabilizing charged-neutral H-bond, while Lys63 from bLF formed two more such stabilizing charged-neutral H-bond with DC-SIGN. The prime binding sites in DC-SIGN; Arg37 and Gln34 occupy helices. The binding pockets in DC-SIGN may be blocked by bLF spontaneously, to hinder their interaction with gp120. No ionic-ionic interaction was observed from gp120_DCSIGN complex. 88th residue, which was a predominant residue in the binding pocket was found to experience a conformational shift from coils to sheets after interaction of DC-SIGN with bLF. This would instigate the pharmaceutical research as non-toxic LF would be economic as a remarkable peptide inhibitor opposing HIV.

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