scholarly journals Genes Identification, Molecular Docking and Dynamics Simulation Analysis of Laccases from Amylostereum areolatum Provides Molecular Basis of Laccase Bound to Lignin

2020 ◽  
Vol 21 (22) ◽  
pp. 8845
Author(s):  
Ningning Fu ◽  
Jiaxing Li ◽  
Ming Wang ◽  
Lili Ren ◽  
Youqing Luo
Keyword(s):  
Molecular Docking ◽  
Molecular Basis ◽  
Simulation Analysis ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Amino Acid Residues ◽  
Sirex Noctilio ◽  
Mutualistic Relationship ◽  
Laccase Genes ◽  
Molecular Docking And Dynamics

An obligate mutualistic relationship exists between the fungus Amylostereum areolatum and woodwasp Sirex noctilio. The fungus digests lignin in the host pine, providing essential nutrients for the growing woodwasp larvae. However, the functional properties of this symbiosis are poorly described. In this study, we identified, cloned, and characterized 14 laccase genes from A. areolatum. These genes encoded proteins of 508 to 529 amino acids and contained three typical copper-oxidase domains, necessary to confer laccase activity. Besides, we performed molecular docking and dynamics simulation of the laccase proteins in complex with lignin compounds (monomers, dimers, trimers, and tetramers). AaLac2, AaLac3, AaLac6, AaLac8, and AaLac10 were found that had low binding energies with all lignin model compounds tested and three of them could maintain stability when binding to these compounds. Among these complexes, amino acid residues ALA, GLN, LEU, PHE, PRO, and SER were commonly present. Our study reveals the molecular basis of A. areolatum laccases interacting with lignin, which is essential for understanding how the fungus provides nutrients to S. noctilio. These findings might also provide guidance for the control of S. noctilio by informing the design of enzyme mutants that could reduce the efficiency of lignin degradation.

scholarly journals Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2071
Author(s):  
Syed Sayeed Ahmad ◽  
Meetali Sinha ◽  
Khurshid Ahmad ◽  
Mohammad Khalid ◽  
Inho Choi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Md Simulation ◽  
Simulation Analysis ◽  
Dynamics Simulation ◽  
Caspase 8 ◽  
Amino Acid Residues ◽  
The Stability ◽  
Molecular Docking And Dynamics

Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.

scholarly journals Molecular Docking and Dynamics Simulation Study of Hyrtios erectus Isolated Scalarane Sesterterpenes as Potential SARS-CoV-2 Dual Target Inhibitors

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 389
Author(s):  
Sameh S. Elhady ◽  
Reda F. A. Abdelhameed ◽  
Rania T. Malatani ◽  
Abdulrahman M. Alahdal ◽  
Hanin A. Bogari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Protein Complexes ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Main Protease ◽  
Simulation Parameters ◽  
Molecular Docking And Dynamics ◽  
Dual Target

Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presented study, molecular docking, ADME properties and all-atom molecular dynamic (MD) simulation, along with two standard antiviral agents (lopinavir and benzopurpurin-4B), were applied to investigate 15 scalaranes sesterterpenes natural compounds, purified from the Red Sea marine sponge Hyrtios erectus, as potential COVID-19 dual-target inhibitors. Following multi-step docking within COVID-19 main protease and Nsp15 endoribonuclease cavities, nine promising drug-like compounds exhibited higher docking scores as well as better interactions with the target’s crucial residues than those of reference ligands. Compounds 2, 6, 11, and 15, were predicted to simultaneously subdue the activity of the two COVID-19 targets. Dynamics behavior of the best-docked molecules, compounds 15 and 6, within COVID-19 target pockets showed substantial stability of ligand-protein complexes as presented via several MD simulation parameters. Furthermore, calculated free-binding energies from MD simulation illustrated significant ligand’s binding affinity towards respective target pockets. All provided findings supported the utility of scalarane-based sesterterpenes, particularly compounds 15 and 6, as promising lead candidates guiding the development of effective therapeutics against SARS-CoV-2.

Synthesis, Molecular Docking and Dynamics Simulation Studies of New 7-oxycoumarin Derivatives as Potential Antioxidant Agents

2018 ◽  
Vol 18 (18) ◽  
pp. 1572-1587
Author(s):  
Nehad A. Abdel Latif ◽  
Rasha Z. Batran ◽  
Salwa F. Mohamed ◽  
Mohammed A. Khedr ◽  
Mohamed I. Kobeasy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Antioxidant Agents ◽  
Molecular Docking And Dynamics

scholarly journals Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis

2021 ◽  
Vol 14 (4) ◽  
pp. 357
Author(s):  
Magdi E. A. Zaki ◽  
Sami A. Al-Hussain ◽  
Vijay H. Masand ◽  
Siddhartha Akasapu ◽  
Sumit O. Bajaj ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Simulation Analysis ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Dynamics Simulation ◽  
Multilinear Regression ◽  
Qsar Analysis ◽  
Main Protease

Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

scholarly journals Phloroglucinol as a Potential Candidate against Trypanosoma congolense Infection: Insights from In Vivo, In Vitro, Molecular Docking and Molecular Dynamic Simulation Analyses

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 469
Author(s):  
Nasirudeen Idowu Abdulrashid ◽  
Suleiman Aminu ◽  
Rahma Muhammad Adamu ◽  
Nasir Tajuddeen ◽  
Murtala Bindawa Isah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Sub Saharan Africa ◽  
Dynamics Simulation ◽  
Potential Candidate ◽  
Inhibitory Effects ◽  
Hydrogen Bond Interaction

Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A2 (PLA2) were investigated. Treatment with phloroglucinol for 14 days significantly (p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense-associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of −4.9 and −5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (−67.84 ± 0.50 kJ/mol) than PLA2-phloroglucinol complex (−77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA2-phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA2.

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