De Novo Protein Structure Prediction

Hung, Ling‐Hong; Ngan, Shing-Chung; Samudrala, Ram

doi:10.1007/978-0-387-68825-1_2

Cited by 9 publications

(10 citation statements)

References 82 publications

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“…A de novo model of the EL5 from WaaL EcK12 was generated by the protinfo server of the University of Washington (Hung et al. , 2005; 2007) using as input the sequence of residues Asn‐259 to Lys‐347 (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Functional analysis of the large periplasmic loop of the Escherichia coli K‐12 WaaL O‐antigen ligase

Pérez

McGarry

Marolda

et al. 2008

Molecular Microbiology

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SummaryWaaL is a membrane enzyme implicated in ligating undecaprenyl-diphosphate (Und-PP)-linked O antigen to lipid A-core oligosaccharide. We determined the periplasmic location of a large (EL5) and small (EL4) adjacent loops in the Escherichia coli K-12 WaaL. Structural models of the EL5 from the K-12, R1 and R4 E. coli ligases were generated by molecular dynamics. Despite the poor amino acid sequence conservation among these proteins, the models afforded similar folds consisting of two pairs of almost perpendicular a-helices. One a-helix in each pair contributes a histidine and an arginine facing each other, which are highly conserved in WaaL homologues. Mutations in either residue rendered WaaL non-functional, since mutant proteins were unable to restore O antigen surface expression. Replacements of residues located away from the putative catalytic centre and non-conserved residues within the centre itself did not affect ligation. Furthermore, replacing a highly conserved arginine in EL4 with various amino acids inactivates WaaL function, but functionality reappears when the positive charge is restored by a replacement with lysine. These results lead us to propose that the conserved amino acids in the two adjacent periplasmic loops could interact with Und-PP, which is the common component in all WaaL substrates.

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Section: Resultsmentioning

confidence: 99%

Functional analysis of the large periplasmic loop of the Escherichia coli K‐12 WaaL O‐antigen ligase

Pérez

McGarry

Marolda

et al. 2008

Molecular Microbiology

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“…Many of the protein structures that we know today have been obtained through experimentation by X-ray crystallography, NMR spectroscopy or cryo-EM, however, the large amount of proteins, makes these processes require more time and increase costs [161]. Modeling through bioinformatics programs has managed to predict the atomic structure of several proteins from their amino acid sequence, by comparison with known protein structures, commonly called templates, although these do not present an accuracy with traditional techniques, the processes are faster and more economical in addition to providing low resolution data during sequence comparison [162,163]. If the protein studied presents a homolog of known structure, the analysis is easier and the generated model is of higher resolution, but if the homologs do not exist or are not identified, the modeling is constructed from scratch [164].…”

Section: Protein Modelingmentioning

confidence: 99%

Bioinformatics as a Tool for the Structural and Evolutionary Analysis of Proteins

Hernández-Domínguez¹,

Castillo-Ortega²,

García-Esquivel³

et al. 2020

Computational Biology and Chemistry

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This chapter deals with the topic of bioinformatics, computational, mathematics, and statistics tools applied to biology, essential for the analysis and characterization of biological molecules, in particular proteins, which play an important role in all cellular and evolutionary processes of the organisms. In recent decades, with the next generation sequencing technologies and bioinformatics, it has facilitated the collection and analysis of a large amount of genomic, transcriptomic, proteomic, and metabolomic data from different organisms that have allowed predictions on the regulation of expression, transcription, translation, structure, and mechanisms of action of proteins as well as homology, mutations, and evolutionary processes that generate structural and functional changes over time. Although the information in the databases is greater every day, all bioinformatics tools continue to be constantly modified to improve performance that leads to more accurate predictions regarding protein functionality, which is why bioinformatics research remains a great challenge.

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“…The first step in modeling the structure of a protein is de novo (ab initio) modeling of the structure from the amino acid sequence without prior knowledge about the spatial arrangement of the amino acids [77]. This approach predicts a protein's folding based on physical/chemical principles without making use of explicit homolog or template structures in contrast to template-based algorithms.…”

Section: Info Box 5: Molecular Modelingmentioning

confidence: 99%

Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria–human protein interactions

Chowdhury

Happonen

Khakzad

et al. 2020

Med Microbiol Immunol

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A central challenge in infection medicine is to determine the structure and function of host-pathogen protein-protein interactions to understand how these interactions facilitate bacterial adhesion, dissemination and survival. In this review, we focus on proteomics, electron cryo-microscopy and structural modeling to showcase instances where affinity-purification (AP) and cross-linking (XL) mass spectrometry (MS) has advanced our understanding of host-pathogen interactions. We highlight cases where XL-MS in combination with structural modeling has provided insight into the quaternary structure of interspecies protein complexes. We further exemplify how electron cryo-tomography has been used to visualize bacterial-human interactions during attachment and infection. Lastly, we discuss how AP-MS, XL-MS and electron cryo-microscopy and-tomography together with structural modeling approaches can be used in future studies to broaden our knowledge regarding the function, dynamics and evolution of such interactions. This knowledge will be of relevance for future drug and vaccine development programs.

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De Novo Protein Structure Prediction

Cited by 9 publications

References 82 publications

Functional analysis of the large periplasmic loop of the Escherichia coli K‐12 WaaL O‐antigen ligase

Functional analysis of the large periplasmic loop of the Escherichia coli K‐12 WaaL O‐antigen ligase

Bioinformatics as a Tool for the Structural and Evolutionary Analysis of Proteins

Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria–human protein interactions

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