Insights on peptide topology in the computational design of protein ligands: the example of lysozyme binding peptides

2021 ◽  
Author(s):  
Cristina Cantarutti ◽  
M. Cristina Vargas ◽  
Cedrix J. Dongmo Foumthuim ◽  
Mireille Dumoulin ◽  
Sara La Manna ◽  
...  
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Cyclic Peptides ◽  
Computational Design ◽  
Protein Ligands ◽  
Binding Peptides

We compared the ability of in silico generated linear and cyclic peptides to target different binding sites on lysozyme. Results demonstrated that cyclic peptides are optimal for solvent exposed sites, while both topologies can target its pocket.

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 Discovery and Validation of Neuropeptide-Y-Binding Peptides for Sensors

2019 ◽  
Vol 124 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Xingqing Xiao ◽  
Zhifeng Kuang ◽  
B. J. Burke ◽  
Yaroslav Chushak ◽  
Barry L. Farmer ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
In Silico ◽  
Binding Peptides

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.

Abstract 121: Pro-inflammatory Cytokine Ifng Modulates Hepatic Sortilin Expression and Lipid Metabolism.

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
John Pirault ◽  
Konstantinos Polyzos ◽  
Daniel F Ketelhuth ◽  
Göran K Hansson
Keyword(s):  
Lipid Metabolism ◽  
Binding Sites ◽  
In Silico ◽  
In Silico Analysis ◽  
Lipid Uptake ◽  
Regulatory T Lymphocytes ◽  
Inflammatory Conditions ◽  
Ldl Particles ◽  
Inflammatory Milieu

Rationale: Hypercholesterolemia and immunity are two major risk factors for cardiovascular diseases (CVDs). Yet, we reported increased atherosclerosis upon depletion of regulatory T lymphocytes (Tregs). The effect was associated with increased hepatic inflammation and reduction of Sortilin expression and lipid uptake in the liver. Objective: To define how inflammatory milieu in the liver can modulate Sortilin and lipid metabolism. Methods: To reproduce the inflammatory milieu, hepatocytes (AML-12) were treated in vitro with IFNg. Expression of genes and proteins of interest were followed by qPCR and western blot. In silico method was used to find binding sites of signal transducer and activator of transcription (STAT1) on Sortilin, confirmed later by chromatin immune precipitation assays (Chip). Lipid uptake by hepatocytes was assessed via incubation of cells with radioactive lipoproteins. Results: Culture of AML-12 cells with IFNg induced the phosphorylation of STAT1 showing an active signaling pathway. In the same inflammatory conditions, Sort1 mRNA is decreased meanwhile its inhibitor (Atf3) expression is increased. Kinetic experiments revealed the reduction of Sortilin after 12 hours of culture, suggesting a post-transcriptional regulation of Sort1 by STAT1. In silico analysis revealed putative binding sites for STAT1 on Sortilin gene which was confirmed by chromatin immunoprecipitation assay (Chip). IFNg treated hepatocytes that were incubated with radioactive lipoproteins demonstrated a reduced uptake capacity of VLDL and LDL particles compared to control cultures. Conclusion: All together, these results suggest that inflammation through production of IFNg is able to directly modulate the lipid metabolism in hepatocytes by acting on Sortilin expression.

scholarly journals In Silico Generation of Peptides by Replica Exchange Monte Carlo: Docking-Based Optimization of Maltose-Binding-Protein Ligands

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133571 ◽  
Author(s):  
Anna Russo ◽  
Pasqualina Liana Scognamiglio ◽  
Rolando Pablo Hong Enriquez ◽  
Carlo Santambrogio ◽  
Rita Grandori ◽  
...  
Keyword(s):  
Monte Carlo ◽  
In Silico ◽  
Binding Protein ◽  
Maltose Binding Protein ◽  
Replica Exchange ◽  
Protein Ligands ◽  
Replica Exchange Monte Carlo

scholarly journals Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis

2019 ◽  
Author(s):  
Nurbubu T. Moldogazieva ◽  
Daria S. Ostroverkhova ◽  
Nikolai N. Kuzmich ◽  
Vladimir V. Kadochnikov ◽  
Alexander A. Terentiev ◽  
...  
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Disulfide Bonds ◽  
Electrostatic Interactions ◽  
Molecular Mechanisms ◽  
3D Structure ◽  
Scoring Function ◽  
Alpha Fetoprotein ◽  
Ligand Interaction ◽  
Ligand Interactions

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔGbind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

scholarly journals Targeting PirAvp and PirBvp Toxins of Vibrio parahaemolyticus with Oilseed Peptides: An In Silico Approach

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1211
Author(s):  
Joe-Hui Ong ◽  
Wey-Lim Wong ◽  
Fai-Chu Wong ◽  
Tsun-Thai Chai
Keyword(s):  
Complex Formation ◽  
In Silico ◽  
Vibrio Parahaemolyticus ◽  
Water Solubility ◽  
Toxin Binding ◽  
Binding Peptides ◽  
Acute Hepatopancreatic Necrosis Disease ◽  
Hydrolysis Of ◽  
Tryptic Hydrolysis ◽  
Dual Target

Acute hepatopancreatic necrosis disease (AHPND), caused by PirAvp- and PirBvp-releasing Vibrio parahaemolyticus strains, has resulted in massive mortality in shrimp aquaculture. Excessive use of antibiotics for AHPND management has led to antibiotic resistance, highlighting the urgency to search for alternatives. Using an in silico approach, we aimed to discover PirAvp/PirBvp-binding peptides from oilseed meals as alternatives to antibiotics. To search for peptides that remain intact in the shrimp digestive tract, and therefore would be available for toxin binding, we focused on peptides released from tryptic hydrolysis of 37 major proteins from seeds of hemp, pumpkin, rape, sesame, and sunflower. This yielded 809 peptides. Further screening led to 24 peptides predicted as being non-toxic to shrimp, fish, and humans, with thermal stability and low water solubility. Molecular docking on the 24 peptides revealed six dual-target peptides capable of binding to key regions responsible for complex formation on both PirAvp and PirBvp. The peptides (ISYVVQGMGISGR, LTFVVHGHALMGK, QSLGVPPQLGNACNLDNLDVLQPTETIK, ISTINSQTLPILSQLR, PQFLVGASSILR, and VQVVNHMGQK) are 1139–2977 Da in mass and 10–28 residues in length. Such peptides are potential candidates for the future development of peptide-based anti-AHPND agents which potentially mitigate V. parahaemolyticus pathogenesis by intercepting PirAvp/PirBvp complex formation.

scholarly journals Homology Modeling and Characterization of Novel Stress Inducing Genes and their Split Sites Recognition in the Genome of Zebra Fish (Danio Rario) by Employing Special Consensus Pattern Matching Algorithms- using an in-Silico Method.

2019 ◽  
Vol 9 (1) ◽  
pp. 6715-6720
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Pattern Matching ◽  
Binding Sites ◽  
In Silico ◽  
3D Structure ◽  
Transcription Factor Binding Sites ◽  
Heat Shock Transcription Factor ◽  
Zebra Fish ◽  
Transcription Factor 1

Zebra fish has long been considered to be as a strong animal model in biology and modern genetics; however now a days its gaining lot of importance in environmental studies as well. The readily availability of entire genome sequences made to permit carrying out in silico studies at Genomic level. As everyone is known that stress is much more complex and complicated process that involves so much of gene regulations known as up regulation and down regulation, the corresponding stress proteins, broadly known as heat shock proteins. In the current study, the potential transcription factor binding sites were traced out by using bioinformatics tools and about 50 heat shock protein genes were predicted by using special alogorithms using pattern matching and position weight matrices. The 3D structure of DNA-binding domain of HSTF-1 ( Heat Shock Transcription factor-1) which is crucial for regulating heat shot proteins was traced out and builted by using homology modelling methods. The 3D structure of the heat shock transcription factor-1 and together with predicted transcription factor binding sites may be validated in future experimental works which would help us in understanding the complex responsive stress mechanisms lying in Zebra fish.

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