A Basic Protein Comparative Three-Dimensional Modeling Methodological Workflow Theory and Practice

Bitar, Mainá; Franco, Glória Regina

doi:10.1109/tcbb.2014.2325018

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…UCSF Chimera is a tool for the interactive viewing and study of structural features and associated data, including the protein's density. Protein structure analysis (ProSA), a method for identifying flaws in theoretical and empirical protein structures, was one of the tools we employed in our investigation to validate protein structure [ 24 ]. The ProSA web software language is designed to validate atomic structure coordinates based on predictions, and the results are scored according to z score values.…”

Section: Methodsmentioning

confidence: 99%

[Retracted] In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases

Ghazi

Bangash²,

Razzaq³

et al. 2023

BioMed Research International

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Inflammasomes are cytoplasmic intracellular multiprotein complexes that control the innate immune system’s activation of inflammation in response to derived chemicals. Recent advancements increased our molecular knowledge of activation of NLRP3 inflammasomes. Although several studies have been done to investigate the role of inflammasomes in innate immunity and other diseases, structural, functional, and evolutionary investigations are needed to further understand the clinical consequences of NLRP3 gene. The purpose of this study is to investigate the structural and functional impact of the NLRP3 protein by using a computational analysis to uncover putative protein sites involved in the stabilization of the protein-ligand complexes with inhibitors. This will allow for a deeper understanding of the molecular mechanism underlying these interactions. It was found that human NLRP3 gene coexpresses with PYCARD, NLRC4, CASP1, MAVS, and CTSB based on observed coexpression of homologs in other species. The NACHT, LRR, and PYD domain-containing protein 3 is a key player in innate immunity and inflammation as the sensor subunit of the NLRP3 inflammasome. The inflammasome polymeric complex, consisting of NLRP3, PYCARD, and CASP1, is formed in response to pathogens and other damage-associated signals (and possibly CASP4 and CASP5). Comprehensive structural and functional analyses of NLRP3 inflammasome components offer a fresh approach to the development of new treatments for a wide variety of human disorders.

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Section: Methodsmentioning

confidence: 99%

[Retracted] In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases

Ghazi

Bangash²,

Razzaq³

et al. 2023

BioMed Research International

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“…Three-dimensional structures were collected in the Protein Data Bank (PDB) [54]. The sequences without available three-dimensional structures were modeled by homology [55]. We selected the templates for modeling using the NCBI BLAST web interface [56] and built 100 models for each protein using MODELLER [57,58,59].…”

Section: Methodsmentioning

confidence: 99%

A Computational Method to Propose Mutations in Enzymes Based on Structural Signature Variation (SSV)

Mariano

Santos

Machado

et al. 2019

IJMS

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With the use of genetic engineering, modified and sometimes more efficient enzymes can be created for different purposes, including industrial applications. However, building modified enzymes depends on several in vitro experiments, which may result in the process being expensive and time-consuming. Therefore, computational approaches could reduce costs and accelerate the discovery of new technological products. In this study, we present a method, called structural signature variation (SSV), to propose mutations for improving enzymes’ activity. SSV uses the structural signature variation between target enzymes and template enzymes (obtained from the literature) to determine if randomly suggested mutations may provide some benefit for an enzyme, such as improvement of catalytic activity, half-life, and thermostability, or resistance to inhibition. To evaluate SSV, we carried out a case study that suggested mutations in β-glucosidases: Essential enzymes used in biofuel production that suffer inhibition by their product. We collected 27 mutations described in the literature, and manually classified them as beneficial or not. SSV was able to classify the mutations with values of 0.89 and 0.92 for precision and specificity, respectively. Then, we used SSV to propose mutations for Bgl1B, a low-performance β-glucosidase. We detected 15 mutations that could be beneficial. Three of these mutations (H228C, H228T, and H228V) have been related in the literature to the mechanism of glucose tolerance and stimulation in GH1 β-glucosidase. Hence, SSV was capable of detecting promising mutations, already validated by in vitro experiments, that improved the inhibition resistance of a β-glucosidase and, consequently, its catalytic activity. SSV might be useful for the engineering of enzymes used in biofuel production or other industrial applications.

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“…One hundred candidate structures were generated for TcNTH1 and further evaluated regarding a combination of their stereochemical properties and energy profiles, provided by Procheck [ 36 ] and ProSA [ 37 ], respectively. More details of this protocol are described on a previous article [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

Expression and the Peculiar Enzymatic Behavior of the Trypanosoma cruzi NTH1 DNA Glycosylase

et al. 2016

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Trypanosoma cruzi, the etiological agent of Chagas’ disease, presents three cellular forms (trypomastigotes, epimastigotes and amastigotes), all of which are submitted to oxidative species in its hosts. However, T. cruzi is able to resist oxidative stress suggesting a high efficiency of its DNA repair machinery.The Base Excision Repair (BER) pathway is one of the main DNA repair mechanisms in other eukaryotes and in T. cruzi as well. DNA glycosylases are enzymes involved in the recognition of oxidative DNA damage and in the removal of oxidized bases, constituting the first step of the BER pathway. Here, we describe the presence and activity of TcNTH1, a nuclear T. cruzi DNA glycosylase. Surprisingly, purified recombinant TcNTH1 does not remove the thymine glycol base, but catalyzes the cleavage of a probe showing an AP site. The same activity was found in epimastigote and trypomastigote homogenates suggesting that the BER pathway is not involved in thymine glycol DNA repair. TcNTH1 DNA-binding properties assayed in silico are in agreement with the absence of a thymine glycol removing function of that parasite enzyme. Over expression of TcNTH1 decrease parasite viability when transfected epimastigotes are submitted to a sustained production of H2O2.Therefore, TcNTH1 is the only known NTH1 orthologous unable to eliminate thymine glycol derivatives but that recognizes and cuts an AP site, most probably by a beta-elimination mechanism. We cannot discard that TcNTH1 presents DNA glycosylase activity on other DNA base lesions. Accordingly, a different DNA repair mechanism should be expected leading to eliminate thymine glycol from oxidized parasite DNA. Furthermore, TcNTH1 may play a role in the AP site recognition and processing.

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A Basic Protein Comparative Three-Dimensional Modeling Methodological Workflow Theory and Practice

Cited by 6 publications

References 33 publications

[Retracted] In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases

[Retracted] In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases

A Computational Method to Propose Mutations in Enzymes Based on Structural Signature Variation (SSV)

Expression and the Peculiar Enzymatic Behavior of the Trypanosoma cruzi NTH1 DNA Glycosylase

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