scholarly journals MUTANT P21 PEPTIDES COULD ACT AS AN IMPROVED CYCLIN A INHIBITORS FOR CANCER THERAPY: AN IN SILICO VALIDATION

2018 ◽  
pp. 59-64
Author(s):  
Tarun Agarwal ◽  
Nithyanan Annamalai ◽  
Hari Prasad Ronanki ◽  
Sandhya Butty ◽  
Tapas Kumar Maiti ◽  
...  
Keyword(s):  
In Silico ◽  
Interaction Analysis ◽  
Substrate Binding ◽  
Cyclin A ◽  
Peptide Library ◽  
Aqueous Environment ◽  
Discovery Studio ◽  
Mutant Peptide ◽  
Binding Groove ◽  
Insight Into

Objective: The present study delineates the generation of mutant peptide library from a known anticancer peptide, p21 and in silico evaluation for their affinity towards cyclin. A substrate binding groove. Methods: Mutant peptide library was created based on their AntiCP score and was docked with cyclin A using ClusPro2.0 web server. The docked structures were further simulated into an aqueous environment using Gromacs 4.5.6. Visualization was performed using PyMol software and interaction analysis was done using Discovery Studio Visualizer 4.1 Client and LigPlot plus tool. Results: A total of 57 mutant peptides were generated; out of which only 3 namely, K3C (Lys3Cys), K3F (Lys3Phe), and K3W (Lys3Trp) had a greater affinity for cyclin A than WILD p21 peptide (HSKRRLIFS). Molecular dynamic simulation studies showed that the peptides remained docked into the substrate binding groove throughout the run. Among all the peptides, K3C showed a significantly higher negative binding energy with cyclin A as compared to WILD. Conclusion: The overall results suggested that K3C mutant peptide had ~30 % higher affinity towards cyclin A and thus, could further be explored for its anticancer potential. The study also provides an insight into the crucial interactions governing the recognition of substrate binding groove of cyclin A for the development of novel peptide-based anticancer therapeutics.

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Copper–oxygen Dynamics in Tyrosinase

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Sachiko Yanagisawa ◽  
Minoru Kubo ◽  
Genji Kurisu ◽  
Shinobu Itoh
Keyword(s):  
Catalytic Mechanism ◽  
Substrate Binding ◽  
Active Form ◽  
Copper Ion ◽  
Atomic Resolution ◽  
Oxygen Species ◽  
X Ray ◽  
Oxygen Dynamics ◽  
Insight Into ◽  
Copper Centre

To unveil the activation of dioxygen on the copper centre (Cu<sub>2</sub>O<sub>2</sub>core) of tyrosinase, we performed X-ray crystallograpy with active-form tyrosinase at near atomic resolution. This study provided a novel insight into the catalytic mechanism of the tyrosinase, including the rearrangement of copper-oxygen species as well as the intramolecular migration of copper ion induced by substrate-binding.<br>

Novel Thiazole-Based Thiazolidinones as Potent Anti-infective Agents: In silico PASS and Toxicity Prediction, Synthesis, Biological Evaluation and Molecular Modelling

2020 ◽  
Vol 23 (2) ◽  
pp. 126-140 ◽  
Author(s):  
Christophe Tratrat
Keyword(s):  
In Silico ◽  
Antimicrobial Agents ◽  
Target Identification ◽  
Biological Evaluation ◽  
Microbial Infection ◽  
Toxicity Prediction ◽  
Discovery Studio ◽  
Bacteria And Fungi ◽  
Multiple Drugs ◽  
Antibacterial And Antifungal

Aims and Objective: The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated. Materials and Methods: The preparation of the substituted 5-benzylidene-2-thiazolyimino-4- thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi strains. Minimum inhibitory concentration and minimum bacterial concentration were both determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the title compounds. Results: PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone hybrids. All tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective molecular target identification and revealed favorable interaction with the target enzymes E. coli MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active compounds was found toxic. Conclusion: Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and may find a potential therapeutic use to eradicate infectious diseases.

scholarly journals In Silico Molecular Docking and Interaction Analysis of Traditional Chinese Medicines Against SARS-CoV-2 Receptor

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110150
Author(s):  
Gang Li ◽  
Wei Zhou ◽  
Xiurong Zhao ◽  
Ying Xie
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Interaction Analysis ◽  
Herbal Remedies ◽  
Receptor Protein ◽  
Stable Complex ◽  
Traditional Chinese Medicines ◽  
Ligand Interaction ◽  
Chinese Medicines ◽  
In Silico Molecular Docking

The novel coronavirus, 2019-nCoV, has led to a major pandemic in 2020 and is responsible for more than 2.9 million officially recorded deaths worldwide. As well as synthetic anti-viral drugs, there is also a need to explore natural herbal remedies. The Traditional Chinese Medicines (TCMs) system has been used for thousands of years for the prevention, diagnosis, and treatment of several chronic diseases. In this paper, we performed an in silico molecular docking and interaction analysis of TCMs against SARS-CoV-2 receptor RNA-dependent RNA polymerase (RdRp). We obtained the 5 most effective plant compounds which had a better binding affinity towards the target receptor protein. These compounds areforsythoside A, rutin, ginkgolide C, icariside II, and nolinospiroside E. The top-ranked compound, based on docking score, was nolinospiroside, a glycoside found in Ophiopogon japonicas that has antioxidant properties. Protein-ligand interaction analysis discerned that nolinospiroside formed a strong bond between ARG 349 of the protein receptor and the carboxylate group of the ligand, forming a stable complex. Hence, nolinospiroside could be deployed as a lead compound against SARS-CoV-2 infection that can be further investigated for its potential benefits in curbing the viral infection.

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

2021 ◽  
Vol 45 (10) ◽  
pp. 4756-4765
Author(s):  
Daoxing Chen ◽  
Liting Zhang ◽  
Yanan Liu ◽  
Jiali Song ◽  
Jingwen Guo ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Study ◽  
The Impact ◽  
Insight Into

EGFR L792Y/F/H mutation makes it difficult for Osimertinib to recognize ATP pockets.

scholarly journals Rapid discovery of self-assembling peptides with one-bead one-compound peptide library

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pei-Pei Yang ◽  
Yi-Jing Li ◽  
Yan Cao ◽  
Lu Zhang ◽  
Jia-Qi Wang ◽  
...  
Keyword(s):  
Combinatorial Library ◽  
Rapid Identification ◽  
Screening Strategy ◽  
Peptide Library ◽  
Aqueous Environment ◽  
Self Assembling ◽  
Material Sciences ◽  
The One ◽  
Combinatorial Space ◽  
Simple Screening

AbstractSelf-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.

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