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/.

The visualCMAT: A web-server to select and interpret correlated mutations/co-evolving residues in protein families

2018 ◽  
Vol 16 (02) ◽  
pp. 1840005 ◽  
Author(s):  
Dmitry Suplatov ◽  
Yana Sharapova ◽  
Daria Timonina ◽  
Kirill Kopylov ◽  
Vytas Švedas
Keyword(s):  
Rational Design ◽  
Visual Analysis ◽  
Structural Information ◽  
Protein Structures ◽  
Web Server ◽  
Physical Contact ◽  
Protein Families ◽  
Sequence Alignments ◽  
Homologous Proteins ◽  
Correlated Mutations

The visualCMAT web-server was designed to assist experimental research in the fields of protein/enzyme biochemistry, protein engineering, and drug discovery by providing an intuitive and easy-to-use interface to the analysis of correlated mutations/co-evolving residues. Sequence and structural information describing homologous proteins are used to predict correlated substitutions by the Mutual information-based CMAT approach, classify them into spatially close co-evolving pairs, which either form a direct physical contact or interact with the same ligand (e.g. a substrate or a crystallographic water molecule), and long-range correlations, annotate and rank binding sites on the protein surface by the presence of statistically significant co-evolving positions. The results of the visualCMAT are organized for a convenient visual analysis and can be downloaded to a local computer as a content-rich all-in-one PyMol session file with multiple layers of annotation corresponding to bioinformatic, statistical and structural analyses of the predicted co-evolution, or further studied online using the built-in interactive analysis tools. The online interactivity is implemented in HTML5 and therefore neither plugins nor Java are required. The visualCMAT web-server is integrated with the Mustguseal web-server capable of constructing large structure-guided sequence alignments of protein families and superfamilies using all available information about their structures and sequences in public databases. The visualCMAT web-server can be used to understand the relationship between structure and function in proteins, implemented at selecting hotspots and compensatory mutations for rational design and directed evolution experiments to produce novel enzymes with improved properties, and employed at studying the mechanism of selective ligand’s binding and allosteric communication between topologically independent sites in protein structures. The web-server is freely available at https://biokinet.belozersky.msu.ru/visualcmat and there are no login requirements.

Homology modeling using SWISS-Model for Biochemistry I v1

2021 ◽  
Author(s):  
Michael Friedman ◽  
Chris Berndsen
Keyword(s):  
Nucleic Acids ◽  
Homology Modeling ◽  
Homology Modelling ◽  
Protein Structures ◽  
Web Server ◽  
James Madison

Protocol for homology modeling proteins for use in Biochemistry I at James Madison University. Protocol guides students to use the SWISS-Model web server (citations below). Citations for servers: Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F. T., de Beer, T. A. P., Rempfer, C., Bordoli, L., Lepore, R., and Schwede, T. (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296–W303.

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 Rational Design of a Triple-Layered Coaxial Extruder System: in silico and in vitro Evaluations Directed Towards Optimizing Cell Viability

2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Christian Augusto Silva ◽  
Carlos J Cortés-Rodriguez ◽  
Jonas Hazur ◽  
Supachai Reakasame ◽  
Aldo R. Boccaccini
Keyword(s):  
Cell Viability ◽  
In Silico ◽  
Rational Design ◽  
Three Dimensional ◽  
Complex Structures ◽  
Vascular Networks ◽  
Coaxial Nozzle ◽  
Wide Availability ◽  
Cell Functionality

Biofabrication is a rapidly evolving field whose main goal is the manufacturing of three-dimensional (3D) cell-laden constructs that closely mimic tissues and organs. Despite recent advances on materials and techniques directed toward the achievement of this goal, several aspects such as tissue vascularization and prolonged cell functionality are limiting bench-to-bedside translation. Extrusion-based 3D bioprinting has been devised as a promising biofabrication technology to overcome these limitations, due to its versatility and wide availability. Here, we report the development of a triple-layered coaxial nozzle for use in the biomanufacturing of vascular networks and vessels. The design of the coaxial nozzle was first optimized toward guaranteeing high cell viability upon extrusion. This was done with the aid of in silico evaluations and their subsequent experimental validation by investigating the bioprinting of an alginate-based bioink. Results confirmed that the values for pressure distribution predicted by in silico experiments resulted in cell viabilities above 70% and further demonstrated the effect of layer thickness and extrusion pressure on cell viability. Our work paves the way for the rational design of multi-layered coaxial extrusion systems to be used in biofabrication approaches to replicate the very complex structures found in native organs and tissues.

scholarly journals Homology Modeling-Based in Silico Affinity Maturation Improves the Affinity of a Nanobody

2019 ◽  
Vol 20 (17) ◽  
pp. 4187 ◽  
Author(s):  
Xin Cheng ◽  
Jiewen Wang ◽  
Guangbo Kang ◽  
Min Hu ◽  
Bo Yuan ◽  
...  
Keyword(s):  
Homology Modeling ◽  
Rational Design ◽  
Structural Model ◽  
Three Dimensional ◽  
Phage Display Library ◽  
Affinity Maturation ◽  
New Strategy ◽  
Design Protocol ◽  
High Binding Affinity

Affinity maturation and rational design have a raised importance in the application of nanobody (VHH), and its unique structure guaranteed these processes quickly done in vitro. An anti-CD47 nanobody, Nb02, was screened via a synthetic phage display library with 278 nM of KD value. In this study, a new strategy based on homology modeling and Rational Mutation Hotspots Design Protocol (RMHDP) was presented for building a fast and efficient platform for nanobody affinity maturation. A three-dimensional analytical structural model of Nb02 was constructed and then docked with the antigen, the CD47 extracellular domain (CD47ext). Mutants with high binding affinity are predicted by the scoring of nanobody-antigen complexes based on molecular dynamics trajectories and simulation. Ultimately, an improved mutant with an 87.4-fold affinity (3.2 nM) and 7.36 °C higher thermal stability was obtained. These findings might contribute to computational affinity maturation of nanobodies via homology modeling using the recent advancements in computational power. The add-in of aromatic residues which formed aromatic-aromatic interaction plays a pivotal role in affinity and thermostability improvement. In a word, the methods used in this study might provide a reference for rapid and efficient in vitro affinity maturation of nanobodies.

scholarly journals FunClust: a web server for the identification of structural motifs in a set of non-homologous protein structures

2008 ◽  
Vol 9 (S2) ◽  
Author(s):  
Gabriele Ausiello ◽  
Pier Federico Gherardini ◽  
Paolo Marcatili ◽  
Anna Tramontano ◽  
Allegra Via ◽  
...  
Keyword(s):  
Protein Structures ◽  
Web Server ◽  
Structural Motifs ◽  
Homologous Protein

scholarly journals Metal Binding Sites in Plant Soluble Inorganic Pyrophosphatases. An Example of the Use of ROSETTA Design and Hidden Markov Models to Guide the Homology Modeling of Proteins

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Luis Rosales-León Rosales-León ◽  
Eric Edmundo Hernández-Domínguez ◽  
Samantha Gaytán-Mondragón ◽  
Rogelio Rodríguez-Sotres
Keyword(s):  
Homology Modeling ◽  
Metal Binding ◽  
Binding Sites ◽  
In Silico ◽  
Markov Models ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Magnesium Ions ◽  
Three Dimensional Structure ◽  
Metal Binding Sites

In contrast to their counterparts in bacteria and animals the soluble inorganic pyrophosphatases from plant cells are active as monomers. The isoforms 1 and 4 from <em>Arabidopsis thaliana</em> have been characterized with more detail, but their three-dimensional structure is unavailable. Here, a recently published protocol (ROSETTA design-HMMer), is used to guide well-known techniques for homology-modeling, in the production of reliable models for the three-dimensional structure of these two arabidopsis isoforms. Their interaction with magnesium ions and pyrophosphate is analyzed <em>in silico</em>in silico.

scholarly journals Pemodelan Protein dengan Homology Modeling menggunakan SWISS-MODEL

2020 ◽  
Vol 2 (2) ◽  
pp. 65-70
Author(s):  
Noer Komari ◽  
Samsul Hadi ◽  
Eko Suhartono
Keyword(s):  
Protein Structure ◽  
Homology Modeling ◽  
In Silico ◽  
3D Structure ◽  
Three Dimensional ◽  
Structure Model ◽  
3D Protein Structure ◽  
Laboratory Equipment ◽  
Model Visualization ◽  
Structure Of Proteins

The three-dimensional (3D) structure of proteins is necessary to understand the properties and functions of proteins. Determining protein structure by laboratory equipment is quite complicated and expensive. An alternative method to predict the 3D structure of proteins in the in silico method. One of the in silico methods is homology modeling. Homology modeling is done using the SWISS-MODEL server. Proteins that will be modeled in the 3D structure are proteins that do not yet have a structure in the RCSB PDB database. Protein sequences were obtained from the UniProt database with code A0A0B6VWS2. The results showed that there were two models selected, namely model-1 with the PDB code template 1q0e and model-2 with the PDB code template 3gtv. The results of sequence alignment and model visualization show that model-1 and model-2 are identical. The evaluation and assessment of model-1 on the Ramachandran Plot have a Favored area of ??97.36%, a MolProbity score of 0.79, and a QMEAN value is 1.13. Model-1 is a good 3D protein structure model.

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