Global public health has been a critical problem by the sudden increase of the COVID-19 outbreak. The papain-like protease (PLpro) of SARS-CoV-2 is a key promising target for antiviral drug ...development since it plays a pivotal role in viral replication and innate immunity. Here, we employed the all-atom molecular dynamics (MD) simulations and binding free energy calculations based on MM-PB(GB)SA and SIE methods to elucidate and compare the binding behaviors of five inhibitors derived from peptidomimetic inhibitors (VIR250 and VIR251) and naphthalene-based inhibitors (GRL-0617, compound 3, and compound Y96) against SARS-CoV-2 PLpro. The obtained results revealed that all inhibitors interacting within the PLpro active site are mostly driven by vdW interactions, and the hydrogen bond formation in residues G163 and G271 with peptidomimetics and the Q269 residue with naphthalene-based inhibitors was essential for stabilizing the protein–ligand complexes. Among the five studied inhibitors, VIR250 exhibited the most binding efficiency with SARS-CoV-2 PLpro, and thus, it was chosen for the rational drug design. Based on the computationally designed ligand–protein complexes, the replacement of aromatic rings including heteroatoms (e.g., thiazolopyridine) at the P2 and P4 sites could help to improve the inhibitor-binding efficiency. Furthermore, the hydrophobic interactions with residues at P1–P3 sites can be increased by enlarging the nonpolar moieties (e.g., ethene) at the N-terminal of VIR250. We expect that the structural data obtained will contribute to the development of new PLpro inhibitors with more inhibitory potency for COVID-19.
As anticancer peptides (ACPs) have attracted great interest for cancer treatment, several approaches based on machine learning have been proposed for ACP identification. Although existing methods ...have afforded high prediction accuracies, however such models are using a large number of descriptors together with complex ensemble approaches that consequently leads to low interpretability and thus poses a challenge for biologists and biochemists. Therefore, it is desirable to develop a simple, interpretable and efficient predictor for accurate ACP identification as well as providing the means for the rational design of new anticancer peptides with promising potential for clinical application. Herein, we propose a novel flexible scoring card method (FSCM) making use of propensity scores of local and global sequential information for the development of a sequence-based ACP predictor (named iACP-FSCM) for improving the prediction accuracy and model interpretability. To the best of our knowledge, iACP-FSCM represents the first sequence-based ACP predictor for rationalizing an in-depth understanding into the molecular basis for the enhancement of anticancer activities of peptides via the use of FSCM-derived propensity scores. The independent testing results showed that the iACP-FSCM provided accuracies of 0.825 and 0.910 as evaluated on the main and alternative datasets, respectively. Results from comparative benchmarking demonstrated that iACP-FSCM could outperform seven other existing ACP predictors with marked improvements of 7% and 17% for accuracy and MCC, respectively, on the main dataset. Furthermore, the iACP-FSCM (0.910) achieved very comparable results to that of the state-of-the-art ensemble model AntiCP2.0 (0.920) as evaluated on the alternative dataset. Comparative results demonstrated that iACP-FSCM was the most suitable choice for ACP identification and characterization considering its simplicity, interpretability and generalizability. It is highly anticipated that the iACP-FSCM may be a robust tool for the rapid screening and identification of promising ACPs for clinical use.
Owing to their ability to maintain a thermodynamically stable fold at extremely high temperatures, thermophilic proteins (TTPs) play a critical role in basic research and a variety of applications in ...the food industry. As a result, the development of computation models for rapidly and accurately identifying novel TTPs from a large number of uncharacterized protein sequences is desirable. In spite of existing computational models that have already been developed for characterizing thermophilic proteins, their performance and interpretability remain unsatisfactory. We present a novel sequence-based thermophilic protein predictor, termed SCMTPP, for improving model predictability and interpretability. First, an up-to-date and high-quality dataset consisting of 1853 TPPs and 3233 non-TPPs was compiled from published literature. Second, the SCMTPP predictor was created by combining the scoring card method (SCM) with estimated propensity scores of g-gap dipeptides. Benchmarking experiments revealed that SCMTPP had a cross-validation accuracy of 0.883, which was comparable to that of a support vector machine-based predictor (0.906-0.910) and 2-17% higher than that of commonly used machine learning models. Furthermore, SCMTPP outperformed the state-of-the-art approach (ThermoPred) on the independent test dataset, with accuracy and MCC of 0.865 and 0.731, respectively. Finally, the SCMTPP-derived propensity scores were used to elucidate the critical physicochemical properties for protein thermostability enhancement. In terms of interpretability and generalizability, comparative results showed that SCMTPP was effective for identifying and characterizing TPPs. We had implemented the proposed predictor as a user-friendly online web server at http://pmlabstack.pythonanywhere.com/SCMTPP in order to allow easy access to the model. SCMTPP is expected to be a powerful tool for facilitating community-wide efforts to identify TPPs on a large scale and guiding experimental characterization of TPPs.
•MEA is a moderately stable amine with Good CO2 capture properties.•MEA is very prone to corrosion and inhibitors may reduce it.•The oxidation is the dominant type of degradation for MEA.•Chelating ...agents and radical scavengers seems to be helpful in oxidation reduction.
Post-combustion Carbon dioxide (CO2) capture (PCC) via amine absorption-stripping is an evolving technology towards mitigation of CO2 emissions. One of the major challenges in the technology development is the suitability of the solvent. Under the process operating conditions, irreversible reactions occur, thereby degrading the amine. The consequences of amine degradation are inevitable. The degradation products are harmful to the environment, increase the corrosion in the process equipment, cause fouling and ultimately make the process inefficient, hazardous and expensive. Monoethanolamine (MEA) is the benchmark solvent used and tested at industrial level for CO2 capture because of its high absorption rate and capacity to capture CO2 as well as medium to high resistance against oxidative and thermal degradation. This review reports degradation of MEA under process operating conditions, which includes up-to-dated list of degradation products, degradation kinetics and degradation pathways. Furthermore, degradation inhibition, computational studies, corrosivity as well as environmental concerns regarding the emissions of amine degradation products are critically reviewed. The objective of study is to provide researchers with a comprehensive knowledge on degradation of MEA, ways to reduce degradation, corrosion inhibition and understanding of environmental concerns for development of models for better understanding of behaviour of MEA and knowledge gaps.
Pesticide remediation with cyclodextrins: a review Waris, Kausar Hayat; Lee, Vannajan Sanghiran; Mohamad, Sharifah
Environmental science and pollution research international,
09/2021, Letnik:
28, Številka:
35
Journal Article
Recenzirano
The aim of this review is to highlight and provide an update on the current development of pesticide remediation methods, focusing on the utilization of different cyclodextrin (CD) molecules. Because ...of less environmental impact and non-toxic nature, CDs are beneficial for pesticide remediation, reducing environmental risk and health hazards. They are advantageous for the removal of pesticides from contaminated areas, as well as for better pesticide formulation and, posing significant effects on the hydrolysis or degradation of pesticides. The review focuses on the current trend and innovations regarding the methods and strategies employed for using CDs in designing pesticide remediation. Nowadays, in addition to the conventional experimental techniques, molecular simulation approaches are significantly contributing to the study of such phenomena and hence are recognized as a widely used tool.
Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, ...the development of an anti-DENV drug is urgently required. Cordycepin (3′-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.
Several anti-HIV scaffolds have been proposed as complementary treatments to highly active antiretroviral therapy. Ank
1D4, a designed ankyrin repeat protein, formerly demonstrated anti-HIV-1 ...replication by interfering with HIV-1 Gag polymerization. However, the improvement of the effectiveness was considered. Recently, the dimeric molecules of Ank
1D4 were accomplished in enhancing the binding activity against HIV-1 capsid (CAp24). In this study, the interaction of CAp24 against the dimer conformations was elucidated to elaborate the bifunctional property. The accessibility of the ankyrin binding domains was inspected by bio-layer interferometry. By inverting the second module of dimeric ankyrin (Ank
1D4
), the CAp24 interaction K
was significantly reduced. This reflects the capability of Ank
1D4
in simultaneously capturing CAp24. On the contrary, the binding activity of dimeric Ank
1D4
was indistinguishable from the monomeric Ank
1D4. The bifunctional property of Ank
1D4
was subsequently confirmed in the secondary reaction with additional p17p24. This data correlates with the MD simulation, which suggested the flexibility of the Ank
1D4
structure. The CAp24 capturing capacity was influenced by the distance of the Ank
1D4 binding domains to introduce the avidity mode of Ank
1D4
. Consequently, Ank
1D4
showed superior potency in interfering with HIV-1 NL4-3 WT and HIV-1 NL4-3 MIR
replication than Ank
1D4
and an affinity improved Ank
1D4-S45Y.
•The complete mechanism of CRR on various TM-DVBNs was investigated by DFT.•TM dopings change the pathway, product selectivity, and activity of the catalyst.•Ni-DVBN and Pd-DVBN produce CH3OH, but ...other TM-DVBNs produce HCOOH and CH4.•The ΔGOH, the universal descriptor, and ICOHP are activity indicators.•Ni-DVBN is the most promising CRR catalyst with the highest activity and selectivity.•Divacancy improves the CRR activity and selectivity compared to a single vacancy.
Single-atom catalysts have recently emerged as a promising approach for catalyzing the electrochemical CO2 reduction reaction (CRR). Transition metal (TM) atom doping to 2-dimensional layer material has been studied for CRR, but compared to studies on TM doped single vacancy (TM-SV) sites, those on double vacancies (TM-DV) sites are minor. In this research, we investigated the doping of 26 (3d-, 4d-, and 5d-groups) TM atoms to the DV of boron nitride nanosheets (BN) using the dispersion-corrected density functional theory method for the complete CRR mechanism. We analyzed the limiting potential of the reactions of different TM-DVBN using the integrated crystal orbital Hamiltonian partition (ICOHP) of TM–O binding, universal descriptor, charge, and the number of valence electrons. We found the volcano plot model which suggests that a moderate OH binding energy of around −0.50 eV, the universal descriptor value around 9.40, and the ICOHP descriptor around −0.20 will provide the lowest limiting potential for CRR. From these studies, we find Ni-DVBN is the most reactive and can produce CH3OH at −0.48 V. This is much better than Ni-SVBN, which requires −1.0 V to produce HCOOH also lower than Fe-SVBN (−0.52 V), which was the best catalyst in the previous study of TM-SVBN. This shows that Ni doping to DVBN is more effective for CRR compared to doping to SVBN.
There is an increasing demand in developing new, effective, and affordable anti-cancer against colon and rectal. In this study, our aim is to identify the potential anthraquinone compounds from the ...root bark of Morinda citrifolia to be tested in vitro against colorectal cancer cell lines. Eight potential anthraquinone compounds were successfully isolated, purified and tested for both in-silico and in-vitro analyses. Based on the in-silico prediction, two anthraquinones, morindone and rubiadin, exhibit a comparable binding affinity towards multitargets of beta-catenin, MDM2-p53 and KRAS. Subsequently, we constructed a 2D interaction analysis based on the above results and it suggests that the predicted anthraquinones from Morinda citrifolia offer an attractive starting point for potential antiproliferative agents against colorectal cancer. In vitro analyses further indicated that morindone and damnacanthal have significant cytotoxicity effect and selectivity activity against colorectal cancer cell lines.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•New sensor based on fluorescein dithio-cyclic skeleton was prepared.•Sensor can utilize in aqueous buffer solutions.•Sensor binds to Hg2+, indicated by fluorescence quenching and color ...change.•Sensor is a Hg2+ “visual-eye” indicator by color change from yellow to orange.•Sensor shows high Hg2+-sensitivity and selectivity with detection limit of 1.5ppb.
A new fluorescent sensor (FC4) based on fluorescein dithia-cyclic skeleton was designed and prepared as a fluoroionophore for the optical and visual-eye detections of Hg2+ in aqueous buffer solution. FC4 was prepared via Kornblum oxidation, ester hydrolysis, alkylation, imine formation and imine reduction. The sensor provided highly sensitive and selective ON–OFF fluorescence sensing toward Hg2+ and was shown to discriminate various interfering metal ions, particularly Cu2+ and Pb2+ as well as Al3+, Ba2+, Ca2+, Cd2+, Fe3+, K+, Mg2+, Mn2+, Na+ and Ni2+. Sensor FC4 also exhibited chromogenic change upon binding to Hg2+, which served as a “visual-eye” indicator which could be observed as a noticeable change of the solution color from yellow to orange. The Hg2+ detection limit of the sensor was 7.38×10−9 or 1.48ppb which was lower than a permissible concentration of Hg2+ in drinking water regulated by the United States Environmental Protection Agency (U.S. EPA).
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