R Statistical Software

Alkarkhi, Abbas F.M.; Alqaraghuli, Wasin A.A.

doi:10.1016/b978-0-12-818622-0.00002-2

Cited by 5 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The energy contribution of each residue was also determined using g_MMPBSA. The graphs from the MM-PBSA computations were generated using the R programming language ( Tippmann, 2014 ; Alkarkhi and Alqaraghuli, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Homology Modeling, de Novo Design of Ligands, and Molecular Docking Identify Potential Inhibitors of Leishmania donovani 24-Sterol Methyltransferase

Sakyi

Broni

Amewu

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The therapeutic challenges pertaining to leishmaniasis due to reported chemoresistance and toxicity necessitate the need to explore novel pathways to identify plausible inhibitory molecules. Leishmania donovani 24-sterol methyltransferase (LdSMT) is vital for the synthesis of ergosterols, the main constituents of Leishmania cellular membranes. So far, mammals have not been shown to possess SMT or ergosterols, making the pathway a prime candidate for drug discovery. The structural model of LdSMT was elucidated using homology modeling to identify potential novel 24-SMT inhibitors via virtual screening, scaffold hopping, and de-novo fragment-based design. Altogether, six potential novel inhibitors were identified with binding energies ranging from −7.0 to −8.4 kcal/mol with e-LEA3D using 22,26-azasterol and S1–S4 obtained from scaffold hopping via the ChEMBL, DrugBank, PubChem, ChemSpider, and ZINC15 databases. These ligands showed comparable binding energy to 22,26-azasterol (−7.6 kcal/mol), the main inhibitor of LdSMT. Moreover, all the compounds had plausible ligand efficiency-dependent lipophilicity (LELP) scores above 3. The binding mechanism identified Tyr92 to be critical for binding, and this was corroborated via molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The ligand A1 was predicted to possess antileishmanial properties with a probability of activity (Pa) of 0.362 and a probability of inactivity (Pi) of 0.066, while A5 and A6 possessed dermatological properties with Pa values of 0.205 and 0.249 and Pi values of 0.162 and 0.120, respectively. Structural similarity search via DrugBank identified vabicaserin, daledalin, zanapezil, imipramine, and cefradine with antileishmanial properties suggesting that the de-novo compounds could be explored as potential antileishmanial agents.

show abstract

Section: Methodsmentioning

confidence: 99%

Homology Modeling, de Novo Design of Ligands, and Molecular Docking Identify Potential Inhibitors of Leishmania donovani 24-Sterol Methyltransferase

Sakyi

Broni

Amewu

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The MM-PBSA approach was used to calculate the binding free energies of the complexes, employing both the continuum solvent models and the molecular mechanics extracted from MD simulations. MM-PBSA calculations were carried out using GMXPBSA [ 72 ] script and were statistically analyzed using the R programming package [ 73 ].…”

Section: Methodsmentioning

confidence: 99%

Computational Study on Potential Novel Anti-Ebola Virus Protein VP35 Natural Compounds

et al. 2021

View full text Add to dashboard Cite

Ebola virus (EBOV) is one of the most lethal pathogens that can infect humans. The Ebola viral protein VP35 (EBOV VP35) inhibits host IFN-α/β production by interfering with host immune responses to viral invasion and is thus considered as a plausible drug target. The aim of this study was to identify potential novel lead compounds against EBOV VP35 using computational techniques in drug discovery. The 3D structure of the EBOV VP35 with PDB ID: 3FKE was used for molecular docking studies. An integrated library of 7675 African natural product was pre-filtered using ADMET risk, with a threshold of 7 and, as a result, 1470 ligands were obtained for the downstream molecular docking using AutoDock Vina, after an energy minimization of the protein via GROMACS. Five known inhibitors, namely, amodiaquine, chloroquine, gossypetin, taxifolin and EGCG were used as standard control compounds for this study. The area under the curve (AUC) value, evaluating the docking protocol obtained from the receiver operating characteristic (ROC) curve, generated was 0.72, which was considered to be acceptable. The four identified potential lead compounds of NANPDB4048, NANPDB2412, ZINC000095486250 and NANPDB2476 had binding affinities of −8.2, −8.2, −8.1 and −8.0 kcal/mol, respectively, and were predicted to possess desirable antiviral activity including the inhibition of RNA synthesis and membrane permeability, with the probable activity (Pa) being greater than the probable inactivity (Pi) values. The predicted anti-EBOV inhibition efficiency values (IC50), found using a random forest classifier, ranged from 3.35 to 11.99 μM, while the Ki values ranged from 0.97 to 1.37 μM. The compounds NANPDB4048 and NANPDB2412 had the lowest binding energy of −8.2 kcal/mol, implying a higher binding affinity to EBOV VP35 which was greater than those of the known inhibitors. The compounds were predicted to possess a low toxicity risk and to possess reasonably good pharmacological profiles. Molecular dynamics (MD) simulations of the protein–ligand complexes, lasting 50 ns, and molecular mechanisms Poisson-Boltzmann surface area (MM-PBSA) calculations corroborated the binding affinities of the identified compounds and identified novel critical interacting residues. The antiviral potential of the molecules could be confirmed experimentally, while the scaffolds could be optimized for the design of future novel anti-EBOV chemotherapeutics.

show abstract

“…Normality and homogeneity of the variances were tested using the Shapiro–Wilk test and Bartlett's test, respectively. To evaluate the combined effect of fungus, substrate, and treatment duration on biomass degradation measurements (C.var, L.var, and IVTD.var), a three‐way analysis of variance (ANOVA) was performed using R software (Alkarkhi & Alqaraghuli, 2020 ). Tukey's test was used for multiple comparisons at a significance level of 0.05.…”

Section: Methodsmentioning

confidence: 99%

Optimizing fungal treatment of lignocellulosic agro‐industrial by‐products to enhance their nutritional value

Benaddou,

Hajjaj,

Allali

et al. 2024

Food Science & Nutrition

View full text Add to dashboard Cite

This study delves into the dynamic interaction between various fungal strains, substrates, and treatment durations to optimize the nutritional value of these by‐products. Six fungi, including Penicillium chrysogenum, Fusarium sp., Fusarium oxysporum, Fusarium solani, Penicillium crustosum, and Cosmospora viridescens, were evaluated across three substrates: wheat straw (WS), cedar sawdust (CW), and olive pomace (OP) over treatment periods of 4, 8, and 12 weeks. The study discerned profound impacts of these fungi across multiple parameters, including cellulose variation (C.var), lignin variation (L.var), and in vitro true digestibility variation (IVTD.var). Our results demonstrated that the various fungi had a significant effect on all parameters (p < .001). Noteworthy, F. oxysporum and F. solani emerged as exemplars, displaying notable lignin degradation, cellulose liberation, and IVTD enhancement. Importantly, P. crustosum demonstrated substantial cellulose degradation, exhibiting optimal efficacy in just 4 weeks for all substrates. Notably, F. sp. excelled, yielding favorable results when treating WS. P. chrysogenum achieved optimal outcomes with 8‐week treatment for WS. Both Fusarium sp. and P. chrysogenum exhibited slight cellulose release, with remarkable reduction of WS lignin compared to other substrates. Especially, WS and OP displayed superior digestibility enhancements relative to CW. It should be noted that the treatment duration further shaped these outcomes, as prolonged treatment (12 weeks) fostered greater benefits in lignin degradation and digestibility, albeit with concomitant cellulose degradation. These findings underscore the intricate balance between fungal strains, substrates, and treatment durations in optimizing the nutritional value of lignocellulosic agro‐industrial by‐products. The outcomes of this study lead to the enhancement in the overall value of by‐products, promoting sustainable livestock feed and advancing agricultural sustainability.

show abstract

R Statistical Software

Cited by 5 publications

References 0 publications

Homology Modeling, de Novo Design of Ligands, and Molecular Docking Identify Potential Inhibitors of Leishmania donovani 24-Sterol Methyltransferase

Homology Modeling, de Novo Design of Ligands, and Molecular Docking Identify Potential Inhibitors of Leishmania donovani 24-Sterol Methyltransferase

Computational Study on Potential Novel Anti-Ebola Virus Protein VP35 Natural Compounds

Optimizing fungal treatment of lignocellulosic agro‐industrial by‐products to enhance their nutritional value

Contact Info

Product

Resources

About