Insight into the impact of EGFR L792Y/F/H mutations on sensitivity to osimertinib: an in silico study

In most of the pathogenic organisms including Plasmodium falciparum, isoprenoids are synthesized via MEP (MethylErythritol 4-Phosphate) pathway. LytB is the last enzyme of this pathway which catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Since the MEP pathway is not used by humans, it represents an attractive target for the development of new antimalarial compounds or inhibitors. Here a systematic in-silico study has been conducted to get an insight into the structure of Plasmodium lytB as well as its affinities towards different inhibitors. We used comparative modeling technique to predict the three dimensional (3D) structure of Plasmodium LytB taking E. Coli LytB protein (PDB ID: 3KE8) as template and the model was subsequently refined through molecular dynamics (MD) simulation. A large ligand dataset containing diphospate group was subjected for virtual screening against the target using GOLD 5.2 program. Considering the mode of binding and affinities, 17 leads were selected on basis of binding energies in comparison to its substrate HMBPP (Gold.Chemscore.DG: -20.9734 kcal/mol). Among them, 5 were discarded because of their inhibitory activity towards other human enzymes. The rest 12 potential leads carry all the properties of any "drug like" molecule and the knowledge of Plasmodium LytB inhibitory mechanism which can provide valuable support for the antimalarial inhibitor design in future.

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The Comparison Between the Mutated HuIFN-β 27-101 and the WildType Interferon β: the Comprehensive In Silico Study to Evaluate theEffect of Mutations on IFN-β

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.074 ◽

2019 ◽

Vol 9 (4) ◽

pp. 640-648

Author(s):

Sayed Sharif Balkhi ◽

Zohreh Hojati

Keyword(s):

Molecular Docking ◽

In Silico ◽

Interferon Beta ◽

Human Interferon ◽

Meaningful Relationship ◽

Significant Difference ◽

In Silico Study ◽

The Impact ◽

Life Function

Purpose: Interferon beta (IFN-β) is used to combat multiple sclerosis (MS) disease. CreatingR27T and V101F mutations (mHuIFN-β-27 and mHuIFN-β-101) is one of the tasks performedto improve human interferon beta (HuIFN-β) half-life, function and expression. In this work,the impact of R27T and V101F mutations in recombinant IFN-β on its binding to interferonreceptors were studied by molecular docking.Methods: This work was performed through in silico study. The simulation of mutation wasperformed using the online Rosetta Backrub software and checked using server verify3D.Comparison of access to the solvent of the amino acids in the structures created was performedusing the asaview online server. Also, the effect of mutations on the fold of the protein wasreviewed by the online HOPE server. The molecular docking was performed between HuIFN-βand the external region of IFNAR receptor using the online ClusPro2 protein-protein dockingserver.Results: The comparison of the values of the negative binding energy (ΔGbind) obtained fromprotein-protein molecular docking between IFNAR receptor and HuIFN-β, mHuIFN-β-27,mHuIFN-β-101 and mHuIFN-β-27-101 ligands did not show a significant difference, and thesedifferences do not see any meaningful relationship between them (P > 0.9999).Conclusion: Regarding these results, it can be concluded that these mutations do not have anegative effect on the composition of the complex rHuIFN-β/IFNAR. So, they do not interferewith the binding of the IFN-β to the receptor. It is concluded that the quality of the rHuIFN-β isimproved by introducing these two mutations.<br />

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Insight into potential toxicity mechanisms of melamine: An in silico study

Toxicology ◽

10.1016/j.tox.2011.02.009 ◽

2011 ◽

Vol 283 (2-3) ◽

pp. 96-100 ◽

Cited By ~ 26

Author(s):

Chao Ma ◽

Hong Kang ◽

Qi Liu ◽

Ruixin Zhu ◽

Zhiwei Cao

Keyword(s):

In Silico ◽

Potential Toxicity ◽

In Silico Study ◽

Toxicity Mechanisms ◽

Insight Into

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Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists

International Journal of Molecular Sciences ◽

10.3390/ijms160715405 ◽

2015 ◽

Vol 16 (12) ◽

pp. 15405-15424 ◽

Cited By ~ 11

Author(s):

Filip Fratev ◽

Ivanka Tsakovska ◽

Merilin Al Sharif ◽

Elina Mihaylova ◽

Ilza Pajeva

Keyword(s):

In Silico ◽

In Silico Study ◽

Receptor Interactions ◽

Insight Into

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An insight into the interaction between α-ketoamide- based inhibitor and coronavirus main protease: A detailed in silico study

Biophysical Chemistry ◽

10.1016/j.bpc.2020.106510 ◽

2021 ◽

Vol 269 ◽

pp. 106510

Author(s):

Snehasis Banerjee

Keyword(s):

In Silico ◽

Main Protease ◽

In Silico Study ◽

Insight Into

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Therapeutic Potential of Tuna Backbone Peptide and Its Analogs: An In Vitro and In Silico Study

Molecules ◽

10.3390/molecules26072064 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2064

Author(s):

Varun Gopinatth ◽

Rufa L. Mendez ◽

Elaine Ballinger ◽

Jung Yeon Kwon

Keyword(s):

In Silico ◽

Bioactive Peptides ◽

Therapeutic Potential ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Activity Assay ◽

In Silico Study ◽

The Impact ◽

Potent Inhibitory Activity

Tuna backbone peptide (TBP) has been reported to exert potent inhibitory activity against lipid peroxidation in vitro. Since this bears relevant physiological implications, this study was undertaken to assess the impact of peptide modifications on its bioactivity and other therapeutic potential using in vitro and in silico approach. Some TBP analogs, despite lower purity than the parent peptide, exerted promising antioxidant activities in vitro demonstrated by ABTS radical scavenging assay and cellular antioxidant activity assay. In silico digestion of the peptides resulted in the generation of antioxidant, angiotensin-converting enzyme (ACE), and dipeptidyl peptidase-IV (DPPIV) inhibitory dipeptides. Using bioinformatics platforms, we found five stable TBP analogs that hold therapeutic potential with their predicted multifunctionality, stability, non-toxicity, and low bitterness intensity. This work shows how screening and prospecting for bioactive peptides can be improved with the use of in vitro and in silico approaches.

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In silico study on the impact of heterogeneous narrowing of small airways on spirometry results

10.1183/1393003.congress-2017.pa3008 ◽

2017 ◽

Cited By ~ 1

Author(s):

Adam Polak ◽

Dariusz Wysoczański ◽

Janusz Mroczka

Keyword(s):

In Silico ◽

Small Airways ◽

In Silico Study ◽

The Impact

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Parallel Control of an Artificial Pancreas with Coordinated Insulin, Glucagon, and Rescue Carbohydrate Control Actions

Journal of Diabetes Science and Technology ◽

10.1177/1932296819879093 ◽

2019 ◽

Vol 13 (6) ◽

pp. 1026-1034 ◽

Cited By ~ 1

Author(s):

Vanessa Moscardó ◽

José Luis Díez ◽

Jorge Bondia

Keyword(s):

In Silico ◽

Artificial Pancreas ◽

Specific Patient ◽

Quantization Effect ◽

In Silico Study ◽

New Strategy ◽

Parallel Control ◽

Clinically Significant ◽

Mean Glucose ◽

The Impact

Background: An artificial pancreas with insulin and glucagon delivery has the potential to reduce the risk of hypo- and hyperglycemia in people with type 1 diabetes. However, a maximum dose of glucagon of 1 mg/d is recommended, potentially still requiring rescue carbohydrates in some situations. This work presents a parallel control structure with intrinsic insulin, glucagon, and rescue carbohydrates coordination to overcome glucagon limitations when needed. Methods: The coordinated controller that combines insulin, glucagon, and rescue carbohydrate suggestions (DH-CC-CHO) was compared with the insulin and glucagon delivery coordinated controller (DH-CC). The impact of carbohydrate quantization for practical delivery was also assessed. An in silico study using the UVA-Padova simulator, extended to include exercise and various sources of variability, was performed. Results: DH-CC and DH-CC-CHO performed similarly with regard to mean glucose (126.25 [123.43; 130.73] vs 127.92 [123.99; 132.97] mg/dL, P = .088), time in range (93.04 [90.00; 95.92] vs 92.91 [90.05; 95.75]%, P = .508), time above 180 mg/dL (4.94 [2.72; 7.53] vs 4.99 [2.93; 7.24]%, P = .966), time below 70 mg/dL (0.61 [0.09; 1.75] vs 0.96 [0.23; 2.17]%, P = .1364), insulin delivery (43.50 [38.68; 51.75] vs 42.86 [38.58; 51.36] U/d, P = .383), and glucagon delivery (0.75 [0.40; 1.83] vs 0.76 [0.43; 0.99] mg/d, P = .407). Time below 54 mg/dL was different (0.00 [0.00; 0.05] vs 0.00 [0.00; 0.16]%, P = .036), although non-clinically significant. This was due to the carbs quantization effect in a specific patient, as no statistical difference was found when carbs were not quantized (0.00 [0.00; 0.05] vs 0.00 [0.00; 0.00]%, P = .265). Conclusions: The new strategy of automatic rescue carbohydrates suggestion in coordination with insulin and glucagon delivery to overcome constraints on daily glucagon delivery was successfully evaluated in an in silico proof of concept.

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