An integrated in silico approach to understand protein–protein interactions: human meprin-β with fetuin-A

Most of the developed kinase inhibitor drugs are ATP competitive and suffer from drawbacks such as off-target kinase activity, development of resistance due to mutation in the ATP binding pocket and unfavorable intellectual property situations. Besides the ATP binding pocket, protein kinases have binding sites that are involved in Protein-Protein Interactions (PPIs); these PPIs directly or indirectly regulate the protein kinase activity. Of recent, small molecule inhibitors of PPIs are emerging as an alternative to ATP competitive agents. Rational design of inhibitors for kinase PPIs could be carried out using molecular modeling techniques. In silico tools available for the prediction of hot spot residues and cavities at the PPI sites and the means to utilize this information for the identification of inhibitors are discussed. Moreover, in silico studies to target the Aurora B-INCENP PPI sites are discussed in context. Overall, this chapter provides detailed in silico strategies that are available to the researchers for carrying out structure-based drug design of PPI inhibitors.

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In silico prediction of protein-protein interactions in human macrophages

BMC Research Notes ◽

10.1186/1756-0500-7-157 ◽

2014 ◽

Vol 7 (1) ◽

pp. 157 ◽

Cited By ~ 3

Author(s):

Oussema Souiai ◽

Fatma Guerfali ◽

Slimane Ben Miled ◽

Christine Brun ◽

Alia Benkahla

Keyword(s):

Protein Interactions ◽

In Silico ◽

In Silico Prediction ◽

Protein Protein Interactions ◽

Human Macrophages

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Molecular Structure and Functional Elucidation of IF-3 Protein of Chloroflexus Aurantiacus Involved in Protein Biosynthesis: An In-Silico Approach

10.26434/chemrxiv.14342372.v1 ◽

2021 ◽

Author(s):

Abu Saim Mohammad Saikat

Keyword(s):

Translation Initiation ◽

Protein Interactions ◽

In Silico ◽

Tertiary Structure ◽

Protein Biosynthesis ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Chloroflexus Aurantiacus ◽

Protein Protein Interactions ◽

Functional Interpretation

Chloroflexus aurantiacus is a thermophilic bacterium that produces a multitude of proteins within its genome. Bioinformatics strategies can facilitate comprehending this organism through functional and structural interpretation assessments. This study aimed to allocate the structure and function through an in-silico approach required for bacterial protein biosynthesis. This in-silico viewpoint provides copious properties, including the physicochemical properties, subcellular location, three-dimensional structure, protein-protein interactions, and functional elucidation of the protein (WP_012256288.1). The STRING program is utilized for the explication of protein-protein interactions. The in-silico investigation documented the protein's hydrophilic nature with predominantly alpha (α) helices in its secondary structure. The tertiary-structure model of the protein has been shown to exhibit reasonably high consistency based on various quality assessment methods. The functional interpretation suggested that the protein can act as a translation initiation factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in protein synthesis. This study is bioinformatically examined that the protein (WP_012256288.1) is affiliated in protein biosynthesis as a translation initiation factor IF-3 of C. aurantiacus.

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Structural and Functional Elucidation of IF-3 Protein of Chloroflexus aurantiacus Involved in Protein Biosynthesis: An In-Silico Approach

10.26434/chemrxiv.14342372.v2 ◽

2021 ◽

Author(s):

Abu Saim Mohammad Saikat ◽

Md. Ekhlas Uddin ◽

Tasnim Ahmad ◽

Shahriar Mahmud ◽

Md. Abu Sayeed Imran ◽

...

Keyword(s):

Translation Initiation ◽

Protein Interactions ◽

In Silico ◽

Tertiary Structure ◽

Protein Biosynthesis ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Chloroflexus Aurantiacus ◽

Protein Protein Interactions ◽

Functional Interpretation

Chloroflexus aurantiacus is a thermophilic bacterium that produces a multitude of proteins within its genome. Bioinformatics strategies can facilitate comprehending this organism through functional and structural interpretation assessments.This study aimed to allocate the structure and function through an in-silico approach required for bacterial protein biosynthesis. This in-silico viewpoint provides copious properties, including the physicochemical properties, subcellular location, three-dimensional structure, protein-protein interactions, and functional elucidation of the protein (WP_012256288.1). The STRING program is utilized for the explication of protein-protein interactions. The in-silico investigation documented the protein's hydrophilic nature with predominantly alpha (α) helices in its secondary structure.The tertiary-structure model of the protein has been shown to exhibit reasonably high consistency based on various quality assessment methods.The functional interpretation suggested that the protein can act as a translation initiation factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in protein synthesis. This study is bioinformatically examined that the protein (WP_012256288.1) is affiliated in protein biosynthesis as a translation initiation factor IF-3 of C. aurantiacus.

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Aryloxy Triester Phosphoramidates as Phosphoserine Biocleavable Masking Motifs

10.26434/chemrxiv.10260887 ◽

2019 ◽

Author(s):

Ageo Miccoli ◽

Binar A. Dhiani ◽

Peter J. Thornton ◽

Olivia A. Lambourne ◽

Edward James ◽

...

Keyword(s):

Small Molecules ◽

Protein Interactions ◽

In Silico ◽

Parent Compound ◽

Cellular Protein ◽

Carboxypeptidase Y ◽

Protein Protein Interactions ◽

Enzymatic Assays ◽

Specific Targeting

Many cellular protein-protein interactions (PPIs) are mediated by phosphoserine. The specific targeting of these PPIs by phosphoserine-containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinders its uptake into cells. To address these issues, we herein report the masking of the phosphate group of phosphoserine with biocleavable aryloxy triester phosphoramidate groups. A combination of in vitro enzymatic assays and in silico studies, using carboxypeptidase Y and Hint-1 respectively, showed that the phosphate masking groups are metabolized to release phosphoserine. To probe the applicability of this phosphoserine masking approach, it was applied to a phosphoserine-containing inhibitor of 14-3-3 dimerization, and this generated molecules with improved pharmacological activity in cells compared to their unmasked phosphoserine-containing parent compound. Collectively, the data showcases the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups as an efficient intracellular delivery system for phosphoserine-containing molecules.

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