scholarly journals Some novel insights into the binding of oseltamivir and zanamivir to H5N1 and N9 influenza virus neuraminidases: A homology modeling and flexible docking study

2009 ◽  
Vol 74 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Marija Mihajlovic ◽  
Petar Mitrasinovic
Keyword(s):  
Homology Modeling ◽  
Protein Structures ◽  
Three Dimensional ◽  
Docking Study ◽  
Energy Difference ◽  
Am1 Method ◽  
Free Energies ◽  
Flexible Docking ◽  
Three Dimensional Models ◽  
Binding Free Energies

In the context of the recent pandemic threat by the worldwide spread of H5N1 avian influenza, novel insights into the mechanism of ligand binding and interaction between various inhibitors (zanamivir - ZMV, oseltamivir - OTV, 2,3-didehydro-2-deoxy-N-acetylneuraminic acid - DANA, peramivir - PMV) and neuraminidases (NA) are of vital importance for the structure-based design of new anti-viral drugs. To address this issue, three-dimensional models of H5N1-NA and N9-NA were generated by homology modeling. Traditional residues within the active site throughout the family of NA protein structures were found to be highly conserved in H5N1-NA. A subtle variation between lipophilic and hydrophilic environments in H5N1-NA with respect to N9-NA was observed, thus shedding more light on the high resistance of some H5N1 strains to various NA inhibitors. Based on these models, an ArgusLab4/AScore flexible docking study was performed. The conformational differences between OTV bound to H5N1-NA and OTV bound to N9-NA were structurally identified and quantified. A slight difference of less than 1 kcal mol-1 between the OTV-N9 and OTV-N1 binding free energies is in agreement with the experimentally predicted free energy difference. The conformational differences between ZMV and OTV bound to either H5N1-NA or N9-NA were structurally identified. The binding free energies of the ZMV complexes, being slightly higher than those of OTV, are not in agreement with what was previously proposed using homology modeling. The differences between ZMV and OTV are suggested to be ascribed to the presence/absence of Asn166 in the active cavity of ZMV/OTV in H5N1-NA, and to the presence/absence of Ser165 in the binding site of ZMV/OTV in N9-NA. The charge distribution was evaluated using the semi-empirical AM1 method. The trends of the AM1 charges of the ZMV and OTV side chains in the complexes deviate from those previously reported.

scholarly journals Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-based Study to Predict the Potential Binding Modes and Interactions into EGFR

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6423
Author(s):  
Faisal Almalki ◽  
Ahmed Shawky ◽  
Ashraf Abdalla ◽  
Ahmed Gouda
Keyword(s):  
Similarity Search ◽  
Docking Study ◽  
Binding Modes ◽  
Free Energies ◽  
Binding Characteristics ◽  
High Binding ◽  
Egfr Ligands ◽  
Potential Binding ◽  
Michael Acceptor ◽  
Binding Free Energies

In the current study, a 2D similarity/docking-based study was used to predict the potential binding modes of icotinib, almonertinib, and olmutinib into EGFR. The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. In addition, the results of the docking study of the three drugs into EGFR revealed high binding free energies (Gb = −6.32 to −8.42 kcal/mol) compared to the co-crystallized ligands (Gb = −7.03 to −8.07 kcal/mol). Analysis of the top-scoring poses of the three drugs was done to identify their potential binding modes. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs.

scholarly journals 3D-PP: A Tool for Discovering Conserved Three-Dimensional Protein Patterns

2019 ◽  
Vol 20 (13) ◽  
pp. 3174
Author(s):  
Alejandro Valdés-Jiménez ◽  
Josep-L. Larriba-Pey ◽  
Gabriel Núñez-Vivanco ◽  
Miguel Reyes-Parada
Keyword(s):  
Homology Modeling ◽  
In Silico ◽  
Rational Design ◽  
Protein Structures ◽  
Three Dimensional ◽  
Web Server ◽  
Free Access ◽  
Protein Patterns ◽  
Structural Motifs ◽  
The Web

Discovering conserved three-dimensional (3D) patterns among protein structures may provide valuable insights into protein classification, functional annotations or the rational design of multi-target drugs. Thus, several computational tools have been developed to discover and compare protein 3D-patterns. However, most of them only consider previously known 3D-patterns such as orthosteric binding sites or structural motifs. This fact makes necessary the development of new methods for the identification of all possible 3D-patterns that exist in protein structures (allosteric sites, enzyme-cofactor interaction motifs, among others). In this work, we present 3D-PP, a new free access web server for the discovery and recognition all similar 3D amino acid patterns among a set of proteins structures (independent of their sequence similarity). This new tool does not require any previous structural knowledge about ligands, and all data are organized in a high-performance graph database. The input can be a text file with the PDB access codes or a zip file of PDB coordinates regardless of the origin of the structural data: X-ray crystallographic experiments or in silico homology modeling. The results are presented as lists of sequence patterns that can be further analyzed within the web page. We tested the accuracy and suitability of 3D-PP using two sets of proteins coming from the Protein Data Bank: (a) Zinc finger containing and (b) Serotonin target proteins. We also evaluated its usefulness for the discovering of new 3D-patterns, using a set of protein structures coming from in silico homology modeling methodologies, all of which are overexpressed in different types of cancer. Results indicate that 3D-PP is a reliable, flexible and friendly-user tool to identify conserved structural motifs, which could be relevant to improve the knowledge about protein function or classification. The web server can be freely utilized at https://appsbio.utalca.cl/3d-pp/.

scholarly journals PROCARB: A Database of Known and Modelled Carbohydrate-Binding Protein Structures with Sequence-Based Prediction Tools

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Adeel Malik ◽  
Ahmad Firoz ◽  
Vivekanand Jha ◽  
Shandar Ahmad
Keyword(s):  
Binding Sites ◽  
De Novo ◽  
Solvent Accessibility ◽  
Protein Structures ◽  
Three Dimensional ◽  
Data Bank ◽  
Dimensional Structure ◽  
Carbohydrate Binding ◽  
Structural And Functional Properties ◽  
Three Dimensional Models

Understanding of the three-dimensional structures of proteins that interact with carbohydrates covalently (glycoproteins) as well as noncovalently (protein-carbohydrate complexes) is essential to many biological processes and plays a significant role in normal and disease-associated functions. It is important to have a central repository of knowledge available about these protein-carbohydrate complexes as well as preprocessed data of predicted structures. This can be significantly enhanced by tools de novo which can predict carbohydrate-binding sites for proteins in the absence of structure of experimentally known binding site. PROCARB is an open-access database comprising three independently working components, namely, (i) Core PROCARB module, consisting of three-dimensional structures of protein-carbohydrate complexes taken from Protein Data Bank (PDB), (ii) Homology Models module, consisting of manually developed three-dimensional models of N-linked and O-linked glycoproteins of unknown three-dimensional structure, and (iii) CBS-Pred prediction module, consisting of web servers to predict carbohydrate-binding sites using single sequence or server-generated PSSM. Several precomputed structural and functional properties of complexes are also included in the database for quick analysis. In particular, information about function, secondary structure, solvent accessibility, hydrogen bonds and literature reference, and so forth, is included. In addition, each protein in the database is mapped to Uniprot, Pfam, PDB, and so forth.

Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase Inhibitors

Drug Research ◽  
2018 ◽  
Vol 68 (07) ◽  
pp. 395-402 ◽  
Author(s):  
Subhajit Roy ◽  
Bawneet Narang ◽  
Manish Gupta ◽  
Vikrant Abbot ◽  
Virender Singh ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Docking Studies ◽  
Binding Modes ◽  
Free Energies ◽  
Flexible Docking ◽  
Docking Simulations ◽  
Xanthine Oxidase Inhibitors ◽  
Best Fit ◽  
Insight Into ◽  
Binding Free Energies

AbstractFlexible docking simulations were carried out on a series of isocytosine analogs as xanthine oxidase (XO) inhibitors. This was done by analysing the interaction of these compounds at the active site of XO. The binding free energies of the analogs were calculated using GoldScore. The binding modes of the best-fit conformation were studied, providing some handy important interactions. The results obtained henceforth provided an insight into the pharmacophoric structural requirements for XO inhibition for this class of molecules.

scholarly journals Molecular Docking Study of Some Nitro Diazo Dye Derivatives as Antiviral Candidates of COVID-19

2021 ◽  
pp. 8-15
Author(s):  
Mohammed Hadi Al–Douh ◽  
Elham Abdalrahem Bin Selim ◽  
Hassan Hadi Abdallah ◽  
Hewa Y. Abdullah ◽  
Aisha Khalid Al–Bakri ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Viral Proteins ◽  
Docking Study ◽  
Free Energies ◽  
Molecular Docking Study ◽  
Docking Method ◽  
Diazo Dye ◽  
Diazo Dyes ◽  
Binding Free Energies ◽  
Molecular Docking Method

In this study, the computerized molecular docking method was used to investigate the interactions of five nitro diazo dye derivatives 1-5 with COVID-19, CLpro, RAF and PLpro as very important viral proteins to target the coronavirus SARS-CoV-2. Among the used diazo dyes, compound 5 showed the highest binding free energies and the lowest inhibition constants Ki with all studied proteins, and it exhibits a large effect to inhibit the activities of the RAF and COVID-19. Therefore, compound 5 may be useful as an antiviral candidate that worth more trials for COVID-19 disease. The binding sites of compound 5 with the tested viral proteins were evaluated.

HOMOLOGY MODELING AND MOLECULAR DYNAMICS STUDY OF HUMAN INOSINE TRIPHOSPHATE PYROPHOSPHATASE

2007 ◽  
Vol 06 (01) ◽  
pp. 141-156
Author(s):  
QING-CHUAN ZHENG ◽  
CHIA-CHUNG SUN
Keyword(s):  
Molecular Dynamics ◽  
Homology Modeling ◽  
Important Determinant ◽  
3D Structure ◽  
Docking Study ◽  
Structure Model ◽  
Flexible Docking ◽  
Inosine Triphosphate Pyrophosphatase ◽  
Modeling Techniques ◽  
Molecular Dynamics Methods

With homology-modeling techniques, molecular mechanics and molecular dynamics methods, a 3D structure model of the human inosine triphosphatase (ITPase; EC 3.6.1.19) is created and refined. This model is further assessed by Profile-3D and ProStat, which confirm that the refined model is reliable. With this model, a flexible docking study is performed, and the results indicate that Arg178, Lys19 and Glu44 are three important determinant residues in substrate binding because they have prominent interaction energies with ITP and form strong hydrogen bonds with ITP. In addition, we further find that the P32T substitution alters the α-helices of ITPase but the β-sheets are almost not changed, and the mutation induces the interaction energy between ITPase and ITP to increase, which are consistent with the conclusion predicted by Sumi et al.8 The results from the mutagenesis imply that Pro32 is vital for the catalytic activity.

scholarly journals Recognition of Errors in the Refinement and Validation of Three-Dimensional Structures of AC1 Proteins of Begomovirus Strains by Using ProSA-Web

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Rajneesh Prajapat ◽  
Avinash Marwal ◽  
R. K. Gaur
Keyword(s):  
Structure Prediction ◽  
Structural Model ◽  
Protein Structures ◽  
Three Dimensional ◽  
Docking Study ◽  
3D Models ◽  
Analysis Tool ◽  
Protein Structure Analysis ◽  
Potential Problems ◽  
Potential Ligand

The structural model of begomovirus AC1 protein is useful for understanding biological function at molecular level and docking study. For this study we have used the ProSA program (Protein Structure Analysis) tool to establish the structure prediction and modeling of protein. This tool was used for refinement and validation of experimental protein structures. Potential problems of protein structures based on energy plots are easily seen by ProSA and are displayed in a three-dimensional manner. In the present study we have selected different AC1 proteins of begomovirus strains (YP_003288785, YP_002004579, and YP_003288773) for structural analysis and display of energy plots that highlight potential problems spotted in protein structures. The 3D models of Rep proteins with recognized errors can be effectively used for in silico docking study for development of potential ligand molecules against begomovirus infection.

A DIFFERENT LOOK AT THE QUALITY OF MODELED THREE-DIMENSIONAL PROTEIN STRUCTURES

2008 ◽  
Vol 06 (02) ◽  
pp. 335-345 ◽  
Author(s):  
ALEKSANDAR POLEKSIC ◽  
MARK FIENUP ◽  
JOSEPH F. DANZER ◽  
DEREK A. DEBE
Keyword(s):  
Drug Design ◽  
Homology Modeling ◽  
Binding Site ◽  
Small Molecule ◽  
Binding Sites ◽  
Structure Prediction ◽  
Protein Structures ◽  
Three Dimensional ◽  
Automated Method

Measuring the accuracy of protein three-dimensional structures is one of the most important problems in protein structure prediction. For structure-based drug design, the accuracy of the binding site is far more important than the accuracy of any other region of the protein. We have developed an automated method for assessing the quality of a protein model by focusing on the set of residues in the small molecule binding site. Small molecule binding sites typically involve multiple regions of the protein coming together in space, and their accuracy has been observed to be sensitive to even small alignment errors. In addition, ligand binding sites contain the critical information required for drug design, making their accuracy particularly important. We analyzed the accuracy of the binding sites on two sets of protein models: the predictions submitted by the top-performing CASP7 groups, and the models generated by four widely used homology modeling packages. The results of our CASP7 analysis significantly differ from the previous findings, implying that the binding site measure does not correlate with the traditional model quality measures used in the structure prediction benchmarks. For the modeling programs, the resolution of binding sites is extremely sensitive to the degree of sequence homology between the query and the template, even when the most accurate alignments are used in the homology modeling process.

Plastic replicas as three-dimensional models of pulps

1975 ◽  
Vol 39 (8) ◽  
pp. 544-546
Author(s):  
HL Wakkerman ◽  
GS The ◽  
AJ Spanauf
Keyword(s):  
Three Dimensional ◽  
Dimensional Models ◽  
Three Dimensional Models

Validation of a Belt Model for Prediction of Hub Forces from a Rolling Tire4

2009 ◽  
Vol 37 (2) ◽  
pp. 62-102 ◽  
Author(s):  
C. Lecomte ◽  
W. R. Graham ◽  
D. J. O’Boy
Keyword(s):  
Internal Pressure ◽  
Equations Of Motion ◽  
Three Dimensional ◽  
Prediction Method ◽  
Analytical Models ◽  
Beam Model ◽  
Impedance Boundary ◽  
Bending Waves ◽  
Tire Rotation ◽  
Three Dimensional Models

Abstract An integrated model is under development which will be able to predict the interior noise due to the vibrations of a rolling tire structurally transmitted to the hub of a vehicle. Here, the tire belt model used as part of this prediction method is first briefly presented and discussed, and it is then compared to other models available in the literature. This component will be linked to the tread blocks through normal and tangential forces and to the sidewalls through impedance boundary conditions. The tire belt is modeled as an orthotropic cylindrical ring of negligible thickness with rotational effects, internal pressure, and prestresses included. The associated equations of motion are derived by a variational approach and are investigated for both unforced and forced motions. The model supports extensional and bending waves, which are believed to be the important features to correctly predict the hub forces in the midfrequency (50–500 Hz) range of interest. The predicted waves and forced responses of a benchmark structure are compared to the predictions of several alternative analytical models: two three dimensional models that can support multiple isotropic layers, one of these models include curvature and the other one is flat; a one-dimensional beam model which does not consider axial variations; and several shell models. Finally, the effects of internal pressure, prestress, curvature, and tire rotation on free waves are discussed.

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