Analysis of Potential Binding Sites of 3,5,4′-Trihydroxystilbene (Resveratrol) and trans-3,3′,5,5′-Tetrahydroxy-4′-methoxystilbene (THMS) to the GAPDH Molecule Using a Computational Ligand-Docking Method: Structural and Functional Changes in GAPDH Induced by the Examined Polyphenols

2015 ◽  
Vol 119 (30) ◽  
pp. 9592-9600 ◽  
Author(s):  
Aleksandra Rodacka ◽  
Joanna Strumillo ◽  
Eligiusz Serafin ◽  
Mieczyslaw Puchala
Keyword(s):  
Binding Sites ◽  
Ligand Docking ◽  
Functional Changes ◽  
Docking Method ◽  
Potential Binding

scholarly journals Improving Blind Docking in DOCK6 through an Automated Preliminary Fragment Probing Strategy

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1224
Author(s):  
Paula Jofily ◽  
Pedro G. Pascutti ◽  
Pedro H. M. Torres
Keyword(s):  
Binding Sites ◽  
Search Algorithm ◽  
Pose Prediction ◽  
Success Rates ◽  
Protein Surfaces ◽  
Cavity Detection ◽  
Docking Method ◽  
Potential Binding ◽  
Binding Pockets ◽  
Automated Pipeline

Probing protein surfaces to accurately predict the binding site and conformation of a small molecule is a challenge currently addressed through mainly two different approaches: blind docking and cavity detection-guided docking. Although cavity detection-guided blind docking has yielded high success rates, it is less practical when a large number of molecules must be screened against many detected binding sites. On the other hand, blind docking allows for simultaneous search of the whole protein surface, which however entails the loss of accuracy and speed. To bridge this gap, in this study, we developed and tested BLinDPyPr, an automated pipeline which uses FTMap and DOCK6 to perform a hybrid blind docking strategy. Through our algorithm, FTMap docked probe clusters are converted into DOCK6 spheres for determining binding regions. Because these spheres are solely derived from FTMap probes, their locations are contained in and specific to multiple potential binding pockets, which become the regions that are simultaneously probed and chosen by the search algorithm based on the properties of each candidate ligand. This method yields pose prediction results (45.2–54.3% success rates) comparable to those of site-specific docking with the classic DOCK6 workflow (49.7–54.3%) and is half as time-consuming as the conventional blind docking method with DOCK6.

scholarly journals Connecting Structure with Kinetics of Single-Stranded DNA Fluctuations that Provide Potential Binding Sites for Replication Proteins

2021 ◽  
Vol 120 (3) ◽  
pp. 219a
Author(s):  
Claire Albrecht ◽  
Brett A. Israels ◽  
Chloe Chvatal ◽  
Peter H. von Hippel ◽  
Andrew H. Marcus
Keyword(s):  
Binding Sites ◽  
Replication Proteins ◽  
Single Stranded Dna ◽  
Potential Binding ◽  
Kinetics Of

scholarly journals The Na,K-ATPase-Dependent Src Kinase Signaling Changes with Mesenteric Artery Diameter

2018 ◽  
Vol 19 (9) ◽  
pp. 2489 ◽  
Author(s):  
Lin Zhang ◽  
Christian Aalkjaer ◽  
Vladimir Matchkov
Keyword(s):  
Smooth Muscle ◽  
Binding Sites ◽  
Isometric Force ◽  
Src Kinase ◽  
Ouabain Binding ◽  
Arterial Diameter ◽  
Small Arteries ◽  
Functional Changes ◽  
High Affinity ◽  
Different Diameters

Inhibition of the Na,K-ATPase by ouabain potentiates vascular tone and agonist-induced contraction. These effects of ouabain varies between different reports. In this study, we assessed whether the pro-contractile effect of ouabain changes with arterial diameter and the molecular mechanism behind it. Rat mesenteric small arteries of different diameters (150–350 µm) were studied for noradrenaline-induced changes of isometric force and intracellular Ca2+ in smooth muscle cells. These functional changes were correlated to total Src kinase and Src phosphorylation assessed immunohistochemically. High-affinity ouabain-binding sites were semi-quantified with fluorescent ouabain. We found that potentiation of noradrenaline-sensitivity by ouabain correlates positively with an increase in arterial diameter. This was not due to differences in intracellular Ca2+ responses but due to sensitization of smooth muscle cell contractile machinery to Ca2+. This was associated with ouabain-induced Src activation, which increases with increasing arterial diameter. Total Src expression was similar in arteries of different diameters but the density of high-affinity ouabain binding sites increased with increasing arterial diameters. We suggested that ouabain binding induces more Src kinase activity in mesenteric small arteries with larger diameter leading to enhanced sensitization of the contractile machinery to Ca2+.

scholarly journals An In-Silico Study of Stable and Environment-Friendly Oryza sativa Urease

2020 ◽  
Vol 11 (3) ◽  
pp. 10238-10247
Keyword(s):  
Oryza Sativa ◽  
Binding Sites ◽  
3D Structure ◽  
Crop Productivity ◽  
Environment Friendly ◽  
Potential Binding ◽  
Urease Enzyme ◽  
In Silico Study ◽  
Stable Mutant ◽  
Detrimental Impact

Urea is one of the most extensively used fertilizers in agriculture but has a detrimental impact on the environment. One of the strategies to reduce this impact can be engineering modified plants containing urease enzyme with a considerably higher affinity for urea so that the urea applied in the fields can be significantly reduced. In this study, we have selected Oryza sativa Urease and generated stable mutants having a high affinity for urea. We modeled the 3D structure of the enzyme and identified the potential binding sites by analyzing the binding sites of similar proteins, i.e., 48 urea binding proteins. We found that mutation of Arg578 with Cys near the substrate-binding site of Oryza sativa Urease leads to a stable mutant protein that has a higher binding affinity for urea. This study will lead to a generation of environment-friendly, stable, genetically modified rice crop that consumes lesser urea, without compromising with crop productivity.

scholarly journals Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 542-551 ◽  
Author(s):  
AA Higazi ◽  
RH Upson ◽  
RL Cohen ◽  
J Manuppello ◽  
J Bognacki ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Binding Sites ◽  
Ldl Receptor ◽  
Cell Types ◽  
Surface Proteins ◽  
Single Chain ◽  
Cell Surface Proteins ◽  
Functional Changes ◽  
And Migration

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.

scholarly journals INSILICO STUDIES OF OXIME PRODRUG OF GLICLAZIDE AGAINST SULPHONYLUREA RECEPTORS (SUR 1)

2017 ◽  
Vol 9 (4) ◽  
pp. 100
Author(s):  
Surendran Vijayaraj ◽  
Kannekanti Chaithanya Veena
Keyword(s):  
Binding Sites ◽  
Pancreatic Beta Cells ◽  
Molecular Targets ◽  
Docking Studies ◽  
Docking Analysis ◽  
Potential Binding ◽  
In Silico Study ◽  
Molecular Docking Analysis ◽  
Autodock 4.2

Objective: Objective of the study is to perform a molecular docking analysis of novel oxime prodrug of gliclazide against SUR1 receptor.Methods: Sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of anti-diabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. Oxime prodrug of gliclazide a better soluble derivative of gliclazide is used for enhancement of bioavailability of gliclazide. Autodock 4.2 software was used for docking studies. Ligand 2D structures were drawn using ChemDraw Ultra 7.0. Binding sites, docking poses and interactions of the ligand with SUR1 receptors were studied by pymol software.Results: The docking studies suggest that potential binding sites of oxime prodrug of gliclazide exhibiting all the major interactions such as hydrogen bonding, hydrophobic interaction and electrostatic interaction with GLU43, LEU11, LEU 40, ILE17 GLU 68, GLN72 residues of SUR1. The binding energy of complexes are also found to be minimal forming stable complexes.Conclusion: In silico study of oxime prodrug of gliclazide conforms, the binding of oxime prodrug of glicalzide with SUR1 receptors which effectively controls the release insulin to regulate plasma glucose concentrations. Hence, the oxime prodrug of gliclazide could be a potent anti-diabetic target molecule which may be worth for further in vitro and in vivostudies. 

scholarly journals The Retinoid and Non-Retinoid Ligands of the Rod Visual G Protein-Coupled Receptor

2019 ◽  
Vol 20 (24) ◽  
pp. 6218 ◽  
Author(s):  
Joseph T. Ortega ◽  
Beata Jastrzebska
Keyword(s):  
Drug Discovery ◽  
G Protein ◽  
Binding Sites ◽  
Binding Pocket ◽  
Biologically Active ◽  
Surface Receptors ◽  
Beneficial Effects ◽  
Light Sensing ◽  
Potential Binding ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) play a predominant role in the drug discovery effort. These cell surface receptors are activated by a variety of specific ligands that bind to the orthosteric binding pocket located in the extracellular part of the receptor. In addition, the potential binding sites located on the surface of the receptor enable their allosteric modulation with critical consequences for their function and pharmacology. For decades, drug discovery focused on targeting the GPCR orthosteric binding sites. However, finding that GPCRs can be modulated allosterically opened a new venue for developing novel pharmacological modulators with higher specificity. Alternatively, focus on discovering of non-retinoid small molecules beneficial in retinopathies associated with mutations in rhodopsin is currently a fast-growing pharmacological field. In this review, we summarize the accumulated knowledge on retinoid ligands and non-retinoid modulators of the light-sensing GPCR, rhodopsin and their potential in combating the specific vision-related pathologies. Also, recent findings reporting the potential of biologically active compounds derived from natural products as potent rod opsin modulators with beneficial effects against degenerative diseases related to this receptor are highlighted here.

Study of a highly accurate and fast protein-ligand docking method based on molecular dynamics

2005 ◽  
Vol 17 (14) ◽  
pp. 1627-1641 ◽  
Author(s):  
M. Taufer ◽  
M. Crowley ◽  
D. J. Price ◽  
A. A. Chien ◽  
C. L. Brooks
Keyword(s):  
Molecular Dynamics ◽  
Ligand Docking ◽  
Docking Method
Sign in / Sign up

Export Citation Format

Share Document