In silico evaluation of antidiabetic molecules of the seeds of Swietenia mahagoni Jacq

2017 ◽  
Vol 6 (1) ◽  
pp. 41 ◽  
Author(s):  
L. V. Vigneshwaran ◽  
K. G. Lalitha
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Therapeutic Agent ◽  
Search Method ◽  
Keywords Diabetes Mellitus ◽  
Deciduous Tree ◽  
Binding Modes ◽  
Keywords Diabetes ◽  
Lamarckian Genetic Algorithm ◽  
Swietenia Mahagoni

Diabetes is a chronic metabolic disorder. WHO has projected that India will have around 57 million persons with diabetes by 2025. Swietenia mahagoni Jacq. (Meliaceae) is a large, deciduous tree whose seeds and bark were used for diabetes traditionally. The in silico hyperglycemic activity of the seeds of Swietenia mahagoni Jacq was studied by using AUTODOCK version 4.2 which reveals the putative binding sites of the compound to target protein. Homology modeling was done using MODELLER for the crystal structure of sodium/glucose co-transporter 2(SGLT2). The putative binding modes of compounds were identified using the search method of Lamarckian Genetic Algorithm (LGA).Atomic affinity and electrostatic potential grid maps were calculated using Auto Grid 4.2. From the fallout, we may scrutinize that for successful docking, intermolecular hydrogen bonding and lipophilic interactions between the ligand and the receptor are very essential. The results evolved with the least binding energy ensures that the Oleanolic showed good inhibitory activity and further work may help to develop the compound as an active therapeutic agent for the treatment of hyperglycemia. Keywords: Diabetes mellitus, Swietenia mahagoni Jacq, Docking, Oleanolic acid.

scholarly journals Binding modes of potential anti-prion phytochemicals to PrPC structures in silico

2019 ◽  
Author(s):  
Sandesh Neupane ◽  
Jenisha Khadka ◽  
Sandesh Rayamajhi ◽  
Arti S. Pandey
Keyword(s):  
Steric Hindrance ◽  
Binding Sites ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Surface Glycoprotein ◽  
Binding Modes ◽  
Cell Surface Glycoprotein ◽  
Chain Conformations

Abstract Background: Prion diseases involve the conversion of a normal, cell-surface glycoprotein (PrPC ) into a misfolded pathogenic form (PrPSC ). Cellular assays and in vivo experiments have identified various compounds with anti-prion activity which work through various mechanisms. Structures of PrPC have revealed the protein to occur in a swapped or non-swapped, monomeric or dimeric forms. Binding modes of known anti-prions is either not known, or has been determined with only the non-swapped structures of PrPC . In the current study medicinal phytochemicals from various databases have been docked with PrPC in silico to identify potential anti-prions in comparison with known anti-prion compounds to determine their binding modes and speculate possible mechanisms of inhibition of PrPC to PrPSC . Results: Eleven new phytochemicals were identified based on their binding energies and pharmacokinetic properties. The binding sites and interactions of the known and new anti-prion compounds are similar, and differences in binding modes occur in structures with very subtle differences in side chain conformations. Binding of these compounds poses steric hindrance to neighbouring molecules. Residues shown to be associated with inhibition of PrPC to PrPSC conversion form interactions with most of the compounds. Conclusions: The new compounds are mostly highly hydrophobic and are derivatives of terpenes, sterols and quinones. They might act as potent inhibitors of the PrPC to PrPSC conversion through a combination of steric hindrance and stabilization of structure through ionic/hydrophobic interactions. Their high binding energies coupled with identical binding sites as those of the known compounds, and their ability to cross the blood brain barrier makes these phytochemicals a promising group of compounds for further studies on prevention of PrPC to PrPSC .

Reversibly Sampling Conformations and Binding Modes Using Molecular Darting

2020 ◽  
Author(s):  
Samuel C. Gill ◽  
David Mobley
Keyword(s):  
Monte Carlo ◽  
Ligand Binding ◽  
Binding Sites ◽  
Degrees Of Freedom ◽  
Dynamics Simulation ◽  
Hiv Integrase ◽  
Binding Modes ◽  
System A ◽  
Multiple Binding ◽  
Internal Degrees Of Freedom

<div>Sampling multiple binding modes of a ligand in a single molecular dynamics simulation is difficult. A given ligand may have many internal degrees of freedom, along with many different ways it might orient itself a binding site or across several binding sites, all of which might be separated by large energy barriers. We have developed a novel Monte Carlo move called Molecular Darting (MolDarting) to reversibly sample between predefined binding modes of a ligand. Here, we couple this with nonequilibrium candidate Monte Carlo (NCMC) to improve acceptance of moves.</div><div>We apply this technique to a simple dipeptide system, a ligand binding to T4 Lysozyme L99A, and ligand binding to HIV integrase in order to test this new method. We observe significant increases in acceptance compared to uniformly sampling the internal, and rotational/translational degrees of freedom in these systems.</div>

Inhibitor Binding Sites in the Protein Tyrosine Phosphatase SHP-2

2020 ◽  
Vol 20 (11) ◽  
pp. 1017-1030
Author(s):  
Haonan Zhang ◽  
Zhengquan Gao ◽  
Chunxiao Meng ◽  
Xiangqian Li ◽  
Dayong Shi
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Binding Sites ◽  
Drug Target ◽  
Tyrosine Phosphatase ◽  
Cancer Drug ◽  
Cellular Activity ◽  
Binding Modes ◽  
Inhibitor Binding ◽  
Protein Tyrosine

Protein tyrosine phosphatase 2 (SHP-2) has long been proposed as a cancer drug target. Several small-molecule compounds with different mechanisms of SHP-2 inhibition have been reported, but none are commercially available. Pool selectivity over protein tyrosine phosphatase 1 (SHP-1) and a lack of cellular activity have hindered the development of selective SHP-2 inhibitors. In this review, we describe the binding modes of existing inhibitors and SHP-2 binding sites, summarize the characteristics of the sites involved in selectivity, and identify the suitable groups for interaction with the binding sites.

Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

2020 ◽  
Vol 75 (9-10) ◽  
pp. 353-362
Author(s):  
Begüm Nurpelin Sağlık ◽  
Ahmet Mücahit Şen ◽  
Asaf Evrim Evren ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Effects ◽  
Docking Studies ◽  
Benzimidazole Derivatives ◽  
Binding Modes ◽  
Reference Drug ◽  
In Silico Studies ◽  
New Compounds ◽  
Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

In silico strategies for modeling RNA aptamers and predicting binding sites of their molecular targets

2021 ◽  
pp. 1-10
Author(s):  
Alejandro Escamilla-Gutiérrez ◽  
Rosa María Ribas-Aparicio ◽  
María Guadalupe Córdova-Espinoza ◽  
Juan Arturo Castelán-Vega
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Molecular Targets ◽  
Rna Aptamers

In Silico Study on Retinoid-binding Modes in Human RBP and ApoD Lipocalins

2018 ◽  
Vol 23 (2) ◽  
pp. 158-167
Author(s):  
Ganapathiraman Munussami ◽  
Sriram Sokalingam ◽  
Jung Rae Kim ◽  
Sun-Gu Lee
Keyword(s):  
In Silico ◽  
Binding Modes ◽  
In Silico Study

An in Silico Investigation of Binding Modes and Pathway of APTO-253 on c-KIT G-Quadruplex DNA

2020 ◽  
Author(s):  
Saikat Pal ◽  
Sandip Paul
Keyword(s):  
Cancer Therapy ◽  
In Silico ◽  
Binding Modes ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
The Stability

The stability of c-KIT G-quadruplex DNA by ligands has been a significant concern in the growing field of cancer therapy. Thus, it is very important to understand the mechanism behind...

The search of CAR, AhR, ESRs binding sites in promoters of intronic and intergenic microRNAs

2018 ◽  
Vol 16 (01) ◽  
pp. 1750029 ◽  
Author(s):  
Vladimir Y. Ovchinnikov ◽  
Denis V. Antonets ◽  
Lyudmila F. Gulyaeva
Keyword(s):  
Transcriptional Activation ◽  
Binding Sites ◽  
In Silico ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Regulation Of Gene Expression ◽  
Experimental Studies ◽  
Transcriptional Level ◽  
Aryl Hydrocarbon ◽  
Exogenous Compounds

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Many exogenous compounds or xenobiotics may affect microRNA expression. It is a well-established fact that xenobiotics with planar structure like TCDD, benzo(a)pyrene (BP) can bind aryl hydrocarbon receptor (AhR) followed by its nuclear translocation and transcriptional activation of target genes. Another chemically diverse group of xenobiotics including phenobarbital, DDT, can activate the nuclear receptor CAR and in some cases estrogen receptors ESR1 and ESR2. We hypothesized that such chemicals can affect miRNA expression through the activation of AHR, CAR, and ESRs. To prove this statement, we used in silico methods to find DRE, PBEM, ERE potential binding sites for these receptors, respectively. We have predicted AhR, CAR, and ESRs binding sites in 224 rat, 201 mouse, and 232 human promoters of miRNA-coding genes. In addition, we have identified a number of miRNAs with predicted AhR, CAR, and ESRs binding sites that are known as oncogenes and as tumor suppressors. Our results, obtained in silico, open a new strategy for ongoing experimental studies and will contribute to further investigation of epigenetic mechanisms of carcinogenesis.

scholarly journals Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607

2021 ◽  
Vol 141 (5) ◽  
pp. 697-708
Author(s):  
Yang Shi ◽  
Alexey G. Murzin ◽  
Benjamin Falcon ◽  
Alexander Epstein ◽  
Jonathan Machin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Binding Sites ◽  
Binding Activity ◽  
Cortical Atrophy ◽  
Binding Modes ◽  
Major Site ◽  
Age Related ◽  
Positron Emission

AbstractTau and Aβ assemblies of Alzheimer’s disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the β-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.

Sign in / Sign up

Export Citation Format

Share Document