scholarly journals Modeling SARS-CoV-2 spike/ACE2 protein–protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context

2022 ◽  
Author(s):  
Vincenzo Tragni ◽  
Francesca Preziusi ◽  
Luna Laera ◽  
Angelo Onofrio ◽  
Ivan Mercurio ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Protein Interactions ◽  
Human Protein ◽  
Protein Protein Interactions ◽  
Protein Targets

scholarly journals Theoretical models of inhibitory activity for inhibitors of protein–protein interactions: targeting menin–mixed lineage leukemia with small molecules

MedChemComm ◽  
2017 ◽  
Vol 8 (12) ◽  
pp. 2216-2227 ◽  
Author(s):  
Wiktoria Jedwabny ◽  
Szymon Kłossowski ◽  
Trupta Purohit ◽  
Tomasz Cierpicki ◽  
Jolanta Grembecka ◽  
...  
Keyword(s):  
Small Molecules ◽  
Binding Affinity ◽  
Protein Interactions ◽  
Empirical Model ◽  
Inhibitory Activity ◽  
Theoretical Models ◽  
Mixed Lineage Leukemia ◽  
Protein Protein Interactions ◽  
Model Based ◽  
Dispersion Terms

A computationally affordable, non-empirical model based on electrostatic multipole and dispersion terms successfully predicts the binding affinity of inhibitors of menin–MLL protein–protein interactions.

scholarly journals Engineered pH-Sensitive Protein G / IgG Interaction

2020 ◽  
Author(s):  
Ramesh K. Jha ◽  
Allison Yankey ◽  
Kalifa Shabazz ◽  
Leslie Naranjo ◽  
Nileena Velappan ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Protein Design ◽  
Protein Interactions ◽  
Rational Design ◽  
Protein G ◽  
Acidic Ph ◽  
Protein Protein Interactions ◽  
Natural Interface ◽  
Complex Stimuli ◽  
Igg Purification

ABSTRACTWhile natural protein-protein interactions have evolved to be induced by complex stimuli, rational design of interactions that can be switched-on-demand still remain challenging in the protein design world. Here, we demonstrate a computationally redesigned natural interface for improved binding affinity could further be mutated to adopt a pH switchable interaction. The redesigned interface of Protein G-IgG Fc domain, when incorporated with histidine and glutamic acid on Protein G (PrG-EHHE), showed a switch in binding affinity by 50-fold when pH was altered from mild acidic to mild basic. The wild type (WT) interface only showed negligible switch. The overall binding affinity at mild acidic pH for PrG-EHHE outperformed the WT PrG interaction. The new reagent PrG-EHHE will be revolutionary in IgG purification since the traditional method of using an extreme acidic pH for elution can be circumvented.Abstract Figure

scholarly journals Cost function network-based design of protein–protein interactions: predicting changes in binding affinity

2018 ◽  
Vol 34 (15) ◽  
pp. 2581-2589 ◽  
Author(s):  
Clément Viricel ◽  
Simon de Givry ◽  
Thomas Schiex ◽  
Sophie Barbe
Keyword(s):  
Cost Function ◽  
Binding Affinity ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Function Network

scholarly journals Visualizing Human Protein‐Protein Interactions and Subcellular Localizations on Cell Images Through CellMap

2020 ◽  
Vol 69 (1) ◽  
Author(s):  
Christian Dallago ◽  
Tatyana Goldberg ◽  
Miguel Angel Andrade‐Navarro ◽  
Gregorio Alanis‐Lobato ◽  
Burkhard Rost
Keyword(s):  
Protein Interactions ◽  
Human Protein ◽  
Protein Protein Interactions

scholarly journals Inferring high-confidence human protein-protein interactions

2012 ◽  
Vol 13 (1) ◽  
pp. 79 ◽  
Author(s):  
Xueping Yu ◽  
Anders Wallqvist ◽  
Jaques Reifman
Keyword(s):  
Protein Interactions ◽  
Human Protein ◽  
Protein Protein Interactions ◽  
High Confidence

scholarly journals Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins

2014 ◽  
Vol 112 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Gurkan Guntas ◽  
Ryan A. Hallett ◽  
Seth P. Zimmerman ◽  
Tishan Williams ◽  
Hayretin Yumerefendi ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Protein Design ◽  
Protein Interactions ◽  
Mammalian Cell Culture ◽  
Large Change ◽  
Small Gtpase ◽  
Protein Protein Interactions ◽  
Binding Assays ◽  
Light Stimulation ◽  
Inducible Protein

The discovery of light-inducible protein–protein interactions has allowed for the spatial and temporal control of a variety of biological processes. To be effective, a photodimerizer should have several characteristics: it should show a large change in binding affinity upon light stimulation, it should not cross-react with other molecules in the cell, and it should be easily used in a variety of organisms to recruit proteins of interest to each other. To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa. In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB. Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation. Here, we describe the use of computational protein design, phage display, and high-throughput binding assays to create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation. A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark. We demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.

scholarly journals Predictions of Protein-Protein Interactions in Schistosoma Mansoni

2017 ◽  
Author(s):  
Javona White Bear ◽  
James H. McKerrow
Keyword(s):  
Schistosoma Mansoni ◽  
Language Processing ◽  
Protein Interactions ◽  
Species Interactions ◽  
Human Protein ◽  
Comparative Approach ◽  
Application Framework ◽  
Protein Protein Interactions ◽  
Protease Inhibition ◽  
Human Proteins

AbstractBackgroundSchistosoma mansoni invasion of the human host involves a variety of cross-species protein-protein interactions. The pathogen expresses a diverse arsenal of proteins that facilitate the breach of physical and biochemical barriers present in skin, evasion of the immune system, and digestion of human hemoglobin, allowing schistosomes to reside in the host for years. However, only a small number of specific interactions between S. mansoni and human proteins have been identified. We present and apply a protocol that generates testable predictions of S. mansoni-human protein interactions.MethodsIn this study, we first predict S. mansoni-human protein interactions based on similarity to known protein complexes. Putative interactions were then scored and assessed using several contextual filters, including the use of annotation automatically derived from literature using a simple natural language processing methodology. Our method predicted 7 out of the 10 previously known cross-species interactions.ConclusionsSeveral predictions that warrant experimental follow-up were presented and discussed, including interactions involving potential vaccine candidate antigens, protease inhibition, and immune evasion. The application framework provides an integrated methodology for investigation of host-pathogen interactions and an extensive source of orthogonal data for experimental analysis. We have made the predictions available online for community perusal.Author SummaryThe S. mansoni parasite is the etiological agent of the disease Schistomiasis. However, protein-protein interactions have been experimentally characterized that relate to pathogenesis and establishment of infection. As with many pathogens, the understanding of these interactions is a key component for the development of new vaccines. In this project, we have applied a computational whole-genome comparative approach to aid in the prediction of interactions between S. mansoni and human proteins and to identify important proteins involved in infection. The results of applying this method recapitulate several previously characterized interactions, as well as suggest additional ones as potential therapeutic targets.

scholarly journals Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins’ Mimicry of Human Protein Interactions

2021 ◽  
Vol 15 ◽  
Author(s):  
Hale Yapici-Eser ◽  
Yunus Emre Koroglu ◽  
Ozgur Oztop-Cakmak ◽  
Ozlem Keskin ◽  
Attila Gursoy ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Clinical Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Data Bank ◽  
In Vitro Studies ◽  
Human Protein ◽  
Protein Protein Interactions ◽  
Human Proteins

The first clinical symptoms focused on the presentation of coronavirus disease 2019 (COVID-19) have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins.Methods: Available 11 of the 29 SARS-CoV-2 proteins’ structures have been extracted from Protein Data Bank. HMI-PRED (Host-Microbe Interaction PREDiction), a recently developed web server for structural PREDiction of protein-protein interactions (PPIs) between host and any microbial species, was used to find the “interface mimicry” through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System.Results: Predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control.Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations.

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