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An Analysis of Protein Interaction and Its Methods, Metabolite Pathway and Drug Discovery
Published in Ayodeji Olalekan Salau, Shruti Jain, Meenakshi Sood, Computational Intelligence and Data Sciences, 2022
According to the environment of a broad area of protein, various efficient methods are to be improved to predict protein interactions. Some of the new ethics belong to the existing methods with developed techniques. It helps to know how to use the interpreted methods in experimental processes for the protein interaction prediction [85]. Figure 13.9 shows the encoded genetic method for cross-linking studies of ncAAs for protein interaction with ribosomal interpretation of live cells. It contains the suppressor tRNA with orthogonal AARS charges of ncAAs, that delivers to the ribosome, which incorporates to a responsible in-frame amber codon with nascent protein. In this way cross-linking ncAA characterize the protein features. Protein interaction helps to identify the mechanism of infection, drug development and the solution to the infection with treatment [86]. In protein–protein interaction relates to target regions and it helps to identify the functions and drug design of the proteins [87]. The SIM tool is used to find the site of the protein interaction with the unbounded protein structures [88]. By using interacting and non-interacting pairs of proteins, structural features are classified into binding or unbinding behaviour of proteins [89].
Imaging Cellular Networks and Protein-Protein Interactions In Vivo
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Snehal Naik, Britney L. Moss, David Piwnica-Worms, Andrea Pichler-Wallace
Compared with studies of protein interactions in cultured cells, strategies to interrogate protein-protein interactions in living organisms impose even further constraints on reporter systems and mechanisms of detection. Most strategies for detecting protein-protein interactions in intact cells are based on fusion of the pair of interacting molecules to defined protein elements to reconstitute a biological or biochemical function. Examples of reconstituted activities include activation of transcription, repression of transcription, activation of signal transduction pathways, or reconstitution of a disrupted enzymatic activity (4). A variety of these techniques have been developed to investigate protein-protein interactions in cultured cells. The two-hybrid system is the most widely applied method to identify and characterize protein interactions.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Of the two main types of epigenetic modifications occurring in human tumor cells, DNA methylation (Figure 5.108 and 5.109) and histone deacetylation (Figure 5.109), patterns of methylation are put into place and then maintained by a family of enzymes known as the DNA methyltransferases. At the time of writing, there are four known human DNA methyltransferases, DNMT1, DNMT2, DNMT3A, and DNMT3B, which use a highly conserved catalytic mechanism to methylate cytosine residues. These enzymes engage in a variety of specific protein-protein interactions that determine their functional specificity. For example, DNMT1 is often found associated with the DNA replication machinery, implying a function in the maintenance of DNA methylation patterns, whereas DNMT3A is more likely to be associated with transcription factors. Furthermore, studies on DNMT knock-out cells suggest a significant level of cooperation between individual enzymes, thus introducing an additional level of complexity. At the structural level, DNA methylation inhibits the binding of control proteins such as transcription factors to the promoter regions of genes, thus directly switching off gene expression. Methyl groups can also be removed from DNA by a number of mechanisms, including direct removal of methyl cytosine, or through cytosine deamination followed by removal of thymine from the resulting thymine/guanosine mismatch and then insertion of an unmethylated version using the base-excision repair machinery (BER). Removal of an entire DNA patch followed by insertion of new nucleotides by Nucleotide Excision Repair or mismatch repair (MMR) is also possible. The epigenetic methylation of a cytosine base by the DNA methyltransferase (DNMT) enzymes.
Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
Published in mAbs, 2023
Hristo L. Svilenov, Paolo Arosio, Tim Menzen, Peter Tessier, Pietro Sormanni
It is desirable to prepare antibody therapeutics as concentrated liquid formulations for subcutaneous delivery, but different antibody variants can display highly variable and difficult-to-predict solution properties, including large differences in their viscosity, opalescence, and/or aggregation properties. Therefore, there is broad interest in early-stage assays that can be used for selecting antibody candidates with low risk for possessing undesirable solution properties. Attractive intermolecular interactions, characterized for instance by the self-association parameter (kD) and second virial coefficient (B22), have been shown to correlate to a good extent with viscosity and opalescent behavior at high antibody concentrations.27 There is therefore interest in developing assays capable to measure intermolecular protein–protein interactions with high throughput and consuming a limited amount of sample.
Epitope mapping of anti-drug antibodies to a clinical candidate bispecific antibody
Published in mAbs, 2022
Arthur J. Schick, Victor Lundin, Justin Low, Kun Peng, Richard Vandlen, Aaron T. Wecksler
The epitope mapping workflow was as follows: Purified ADAs from goat and cyno were mixed with BsAb1 to facilitate ADA-BsAb1 complex formation, separated using size-exclusion chromatography (SE-HPLC), and subjected to HRF analysis. SE-HPLC not only enables enrichment of the complexes but also provides buffer exchange into a suitable buffer (phosphate) for HRF analysis. The HRF technology used in this study was Fast Photochemical Oxidation of Proteins (FPOP), a bench-top technology ideally suited for epitope mapping and characterizing protein–protein interactions.18,19 HDX-MS is a well-established technique used in industry for epitope mapping, but as with all bottom-up MS technology, there are certain limitations, including the time-dependent labeling requirements, pH-dependent labeling effects, and deglycosylation challenges. FPOP can circumvent some of these challenges due to the stable addition of the hydroxyl radical.20 However, the combination of both of these technologies may provide the most comprehensive understanding of protein–protein interactions.21–23
Targeting Chikungunya virus by computational approaches: from viral biology to the development of therapeutic strategies
Published in Expert Opinion on Therapeutic Targets, 2020
Vitor Won-Held Rabelo, Izabel Christina Nunes de Palmer Paixão, Paula Alvarez Abreu
The understanding of the protein-protein interaction network and its biological roles may contribute greatly to explain disease mechanisms and developing therapeutic strategies [29]. In this regards, Sharma and coworkers [30] solved the X-ray structure of CHIKV CP and, further, studied the interaction with the glycoprotein E2 by building homology models of the cytosolic domains of gE1 and gE2 and fitting them into a cryo-EM map of the complex CP-E2-E1 from Venezuelan equine encephalitis virus (VEEV). Interestingly, a loop of gE2 interacted with the hydrophobic pocket of CP. In particular, the residue P730 of gE2 seems to be critical for the stabilization of this protein-protein complex because it was involved in a van der Waals interaction network with several CP residues such as V130, G131, D132, V134, M135, W245, and V250. Therefore, this hydrophobic pocket is a potential site to search for protein-protein interaction inhibitors with anti-CHIKV activity.