scholarly journals Molecular docking-based test for affinities of two ligands toward vasopressin and oxytocin receptors.

2001 ◽  
Vol 48 (1) ◽  
pp. 131-135 ◽  
Author(s):  
R Slusarz ◽  
R Kaźmierkiewicz ◽  
A Giełdoń ◽  
B Lammek ◽  
J Ciarkowski
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Ligand Binding ◽  
Effective Procedure ◽  
Amino Acid Residues ◽  
Receptor Ligand ◽  
Docking Simulations ◽  
Oxytocin Receptors ◽  
Developing Area

Molecular docking simulations are now fast developing area of research. In this work we describe an effective procedure of preparation of the receptor-ligand complexes. The amino-acid residues involved in ligand binding were identified and described.

Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Amir Taherkhani ◽  
Athena Orangi ◽  
Shirin Moradkhani ◽  
Zahra Khamverdi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Amino Acid ◽  
Matrix Metalloproteinase ◽  
Ligand Binding ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Dimensional Structure ◽  
Control Test ◽  
Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

scholarly journals In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4147
Author(s):  
Neha Gupta ◽  
Saurav Kumar Choudhary ◽  
Neeta Bhagat ◽  
Muthusamy Karthikeyan ◽  
Archana Chaturvedi
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Guanylyl Cyclase ◽  
Extracellular Domain ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Guanylyl Cyclase C ◽  
Amino Acid Residues ◽  
Lead Compounds

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

scholarly journals Molecular Modification of Fluoroquinolone-Biodegrading Enzymes Based on Molecular Docking and Homology Modelling

2019 ◽  
Vol 16 (18) ◽  
pp. 3407 ◽  
Author(s):  
Liu ◽  
Sun ◽  
Cui ◽  
Ding
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Homology Modelling ◽  
Binding Affinities ◽  
The Novel ◽  
Amino Acid Residues ◽  
Degrading Enzyme ◽  
Degrading Enzymes ◽  
Docking Method ◽  
Degradation Effect

To improve the biodegradation efficiency of fluoroquinolone antibiotics during sewage treatment, fluoroquinolone aerobic, anaerobic and facultative degrading enzymes for fluoroquinolone degradation were modified by molecular docking and homology modelling. First, amino acid residues of the binding sites of degrading enzymes for the target fluoroquinolones ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL) were analysed by the molecular docking method. The hydrophobic amino acid residues within 5 Å of the target fluoroquinolone molecules were selected as the modification sites. The hydrophobic amino acid residues at the modified sites were replaced by the hydrophilic amino acid residues, and 150 amino acid sequence modification schemes of the degrading enzymes were designed. Subsequently, a reconstruction scheme of the degrading enzyme amino acid sequence reconstruction scheme was submitted to the SWISS-MODEL server and a selected homology modelling method was used to build a new structure of the degrading enzyme. At the same time, the binding affinities between the novel degrading enzymes and the target fluoroquinolones (represented by the docking scoring function) were evaluated by the molecular docking method. It was found that the novel enzymes can simultaneously improve the binding affinities for the three target fluoroquinolones, and the degradation ability of the six modification schemes was increased by more than 50% at the same time. Among the novel enzymes, the affinity effect of the novel anaerobic enzyme (6-1) with CIP, NOR and OFL was significantly increased, with increases of 129.24%, 165.06% and 169.59%, respectively, followed by the facultative enzyme and aerobic enzyme. In addition, the designed degrading enzymes had certain selectivity for the degradation of the target quinolone. Among the novel enzymes, the binding affinities of the novel anaerobic enzyme (6-3) and CIP, the novel aerobic enzyme (3-6) and NOR, and the novel facultative enzyme (13-6) and OFL were increased by 149.71%, 178.57% and 297.12% respectively. Calculations using the Gaussian09 software revealed that the degradation reaction barrier of the novel degrading enzyme (7-1) and CIP NOR and OFL decreased by 37.65 kcal·mol−1, 6.28 kcal·mol−1 and 6.28 kcal·mol−1, respectively, which would result in efficient degradation of the target fluoroquinolone molecules. By analysing the binding affinity of the degrading enzymes before and after the modification with methanol, it was further speculated that the degradation effect of the modified aerobic degrading enzymes on organic matter was lower than that before the modification, and the increase or decrease in the degradation effect was less than 10%. The mechanism analysis found that the interaction between the modified amino acid residues of the degrading enzymes and the fluoroquinolone molecules increased. The average distance between the amino acid residues and the fluoroquinolone molecules represented a comprehensive affinity effect, and its value was positively correlated with the degradation effect of the novel degrading enzymes.

A Mutation in the  Subunit of the Platelet Integrin IIbβ3 Identifies a Novel Region Important for Ligand Binding

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 918-924 ◽  
Author(s):  
Eileen Collins Tozer ◽  
Elizabeth K. Baker ◽  
Mark H. Ginsberg ◽  
Joseph C. Loftus
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Single Amino Acid ◽  
Chimeric Receptor ◽  
Amino Acid Residues ◽  
Genetic Approach ◽  
Specific Amino Acid ◽  
Transfected Cells ◽  
Binding Function ◽  
A Cell

Abstract An unbiased genetic approach was used to identify a specific amino acid residue in the IIb subunit important for the ligand binding function of the integrin IIbβ. Chemically mutagenized cells were selected by flow cytometry based on their inability to bind the ligand mimetic antibody PAC1 and a cell line containing a single amino acid substitution in IIb at position 224 (D→V) was identified. Although well expressed on the surface of transfected cells, IIbD224Vβ3 as well as IIbD224Aβ3 did not bind IIbβ3-specific ligands or a RGD peptide, a ligand shared in common with vβ3. Insertion of exon 5 of IIb, residues G193-W235, into the backbone of the v subunit did not enable the chimeric receptor to bind IIbβ3-specific ligands. However, the chimeric receptor was still capable of binding to a RGD affinity matrix. IIbD224 is not well conserved among other integrin  subunits and is located in a region of significant variability. In addition, amino acid D224 lies within a predicted loop of the recently proposed β-propeller model for integrin  subunits and is adjacent to a loop containing amino acid residues previously implicated in receptor function. These data support a role for this region in ligand binding function of the IIbβ3 receptor.

scholarly journals The Differential Binding Affinities of the Luteinizing Hormone (LH)/Choriogonadotropin Receptor for LH and Choriogonadotropin Are Dictated by Different Extracellular Domain Residues

2005 ◽  
Vol 19 (5) ◽  
pp. 1263-1276 ◽  
Author(s):  
Colette Galet ◽  
Mario Ascoli
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Binding Affinity ◽  
Extracellular Domain ◽  
Binding Affinities ◽  
Amino Acid Residues ◽  
Identify Amino Acid ◽  
Β Sheets ◽  
Leucine Rich Repeats ◽  
High Degree

Abstract The high degree of amino acid sequence homology and the divergent ligand binding affinities of the rat (r) and human (h) LH receptors (LHRs) allowed us to identify amino acid residues of their extracellular domain that are responsible for the different binding affinities of bovine (b) and hLH, and human choriogonadotropin (hCG) to the hLHR and rLHR. Because of the proposed importance of the β-sheets of the leucine-rich repeats (LRRs) of the extracellular domain of the LHR on hormone binding, we examined 10 divergent residues present in these regions by analyzing two complementary sets of mutants in which hLHR residues were substituted with the corresponding rLHR residues and vice versa. These experiments resulted in the identification of a single residue (a Ile or Ser in the C-terminal end of LRR2 of the hLHR or rLHR, respectively) that is important for hLH binding affinity. Surprisingly, however, this residue does not affect hCG or for bLH binding affinity. In fact, the results obtained with bLH and hCG show that several of the divergent residues in the β-sheets of LRR1–9 affect bLH binding affinity, but none of them affect hCG binding affinity. Importantly, our results also emphasize the involvement of residues outside of the β-sheets of the LRRs of the LHR in ligand binding affinity. This finding has to be considered in future models of the interaction of LH/CG with the LHR.

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