scholarly journals Alignment of distantly related protein structures: algorithm, bound and implications to homology modeling

2011 ◽  
Vol 27 (18) ◽  
pp. 2537-2545 ◽  
Author(s):  
Sheng Wang ◽  
Jian Peng ◽  
Jinbo Xu
Keyword(s):  
Homology Modeling ◽  
Protein Structures ◽  
Related Protein

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.

Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen

1989 ◽  
Vol 9 (5) ◽  
pp. 2279-2283
Author(s):  
S Jindal ◽  
A K Dudani ◽  
B Singh ◽  
C B Harley ◽  
R S Gupta
Keyword(s):  
Mammalian Cells ◽  
Mitochondrial Protein ◽  
Protein Structures ◽  
Mycobacterial Antigen ◽  
Related Protein ◽  
Bisphosphate Carboxylase ◽  
Oligomeric Protein ◽  
Strong Homology ◽  
Major Antigen ◽  
High Degree

The complete cDNA for a human mitochondrial protein designated P1, which was previously identified as a microtubule-related protein, has been cloned and sequenced. The deduced amino acid sequence of P1 shows strong homology (40 to 50% identical residues and an additional 20% conservative replacements) to the 65-kilodalton major antigen of mycobacteria, to the GroEL protein of Escherichia coli, and to the ribulose 1,5-bisphosphate carboxylase-oxygenase (rubisco) subunit binding protein of plant chloroplasts. Similar to the case with the latter two proteins, which have been shown to act as chaperonins in the posttranslational assembly of oligomeric protein structures, it is suggested that P1 may play a similar role in mammalian cells. The observed high degree of homology between human P1 and mycobacterial antigen also suggests the possible involvement of this protein in certain autoimmune diseases.

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.

Experimental assessment of differences between related protein crystal structures

1999 ◽  
Vol 55 (11) ◽  
pp. 1878-1884 ◽  
Author(s):  
Gerard J. Kleywegt
Keyword(s):  
Crystal Structures ◽  
Electron Density ◽  
Local Density ◽  
Structure Refinement ◽  
Protein Structures ◽  
Biological Significance ◽  
Protein Crystal ◽  
Related Protein ◽  
Density Correlation ◽  
Experimental Electron Density

Prior to attaching any biological significance to differences between two related protein crystal structures, it must be established that such differences are genuine, rather than artefacts of the structure-determination protocol. This will be all the more important as more and more related protein structures are solved and comparative structural biology attempts to correlate structural differences with variations in biological function, activity or affinity. A method has been developed which enables unbiased assessment of differences between the structures of related biomacromolecules using experimental crystallographic information alone. It is based on the use of local density-correlation maps, which contain information regarding the similarity of the experimental electron density for corresponding parts of different copies of a molecule. The method can be used to assess a priori which parts of two or more molecules are likely to be structurally similar; this information can then be employed during structure refinement. Alternatively, the method can be used a posteriori to verify that differences observed in two or more models are supported by the experimental information. Several examples are discussed which validate the notion that local conformational variability is highly correlated to differences in the local experimental electron density.

scholarly journals Flexibility and mobility of SARS-CoV-2-related protein structures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rudolf A. Römer ◽  
Navodya S. Römer ◽  
A. Katrine Wallis
Keyword(s):  
In Silico ◽  
Drug Targets ◽  
Large Scale ◽  
Structural Information ◽  
Protein Structures ◽  
Antiviral Drug ◽  
Docking Studies ◽  
Related Protein

AbstractThe worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of possible SARS-CoV-2 drug targets, as deposited on the Protein Databank (PDB), and ascertain their dynamics, flexibility and rigidity. For example, for the SARS-CoV-2 spike protein—using its complete homo-trimer configuration with 2905 residues—our method identifies a large-scale opening and closing of the S1 subunit through movement of the S$${}^\text{B}$$ B domain. We compute the full structural information of this process, allowing for docking studies with possible drug structures. In a dedicated database, we present similarly detailed results for the further, nearly 300, thus far resolved SARS-CoV-2-related protein structures in the PDB.

scholarly journals SAXSDom: Modeling multi-domain protein structures using small-angle X-ray scattering data

2019 ◽  
Author(s):  
Jie Hou ◽  
Badri Adhikari ◽  
John J. Tanner ◽  
Jianlin Cheng
Keyword(s):  
Homology Modeling ◽  
Small Angle ◽  
Tertiary Structure ◽  
Protein Structures ◽  
Scattering Data ◽  
Multidomain Proteins ◽  
X Ray ◽  
X Ray Scattering ◽  
Domain Protein ◽  
Ray Scattering

AbstractMany proteins are composed of several domains that pack together into a complex tertiary structure. Some multidomain proteins can be challenging for protein structure modeling, particularly those for which templates can be found for the domains but not for the entire sequence. In such cases, homology modeling can generate high quality models of the domains but not for the assembled protein. Small-angle X-ray scattering (SAXS) reports on the solution structural properties of proteins and has the potential for guiding homology modeling of multidomain proteins. In this work, we describe a novel multi-domain protein assembly modeling method, SAXSDom, that integrates experimental knowledge from SAXS profiles with probabilistic Input-Output Hidden Markov model (IOHMM). Four scoring functions to account for the energetic contribution of SAXS restraints for domain assembly were developed and tested. The method was evaluated on multi-domain proteins from two public datasets. Based on the results, the accuracy of domain assembly was improved for 40 out of 46 CASP multi-domain proteins in terms of RMSD and TM-score when SAXS information was used. Our method also achieved higher accuracy for at least 45 out of 73 multi-domain proteins according to RMSD and TM-score metrics in the AIDA dataset. The results demonstrate that SAXS data can provide useful information to improve the accuracy of domain-domain assembly. The source code and tool packages are available at http://github.com/multicom-toolbox/SAXSDom.

Protein modeling by homology using the example of tick-borne encephalitis serine protease NS3

2020 ◽  
pp. 59-66
Author(s):  
Nikita Ilment ◽  
Ekaterina Zinina
Keyword(s):  
Electron Microscopy ◽  
Homology Modeling ◽  
Homology Modelling ◽  
Protein Structures ◽  
3D Structure ◽  
Free Software ◽  
Homologous Proteins ◽  
Cryo Electron Microscopy ◽  
Tick Borne Encephalitis ◽  
Sequences Analysis

Homology modeling is a process of obtaining a 3D structure of a protein using various algorithms based on already known structures of homologous proteins. The spatial structure of protein is required for in silico protein evaluation. 3D structures can be obtained using different methods: NMR, Xray crystallography (XRC), and cryo-electron microscopy (cryo-EM), but these methods require a lot of time and money. At the same time, the speed of nucleotide sequences analysis is increasing, thereby creating a mismatch between the number of decoded genomes and the investigated 3D protein structures that are encoded by these sequences. Also, homology modeling is the easiest and fastest way to obtain the model of the desired protein. This review describes free software for homology modelling — SWISS-MODEL and MODELLER, how to use it and how to evaluate the results.

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/.

A data bank merging related protein structures and sequences

1992 ◽  
Vol 5 (2) ◽  
pp. 121-137 ◽  
Author(s):  
Stefano Pascarella ◽  
Patrick Argos
Keyword(s):  
Protein Structures ◽  
Data Bank ◽  
Related Protein
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