Please, has anyopne used CheckMateTwo-hybrid, Nanobit or Lumit from PROMEGA or PLA Duo Link from Sigma for studying protein interaction and discovery of drug inhibitor of the interaction?
The simple answer to your question is that there is no reliable assay for protein interactions. This failure is founded in the very basis of existing methods - they cannot work. I cover this in some detail in "Making the Case for Functional Proteomics: Methods and Protocols" available here on ResearchGate. As for Two-hybrid methods comparisons, overlap between methods is quite small as demonstrated here: Article An experimentally derived confidence score for binary protei...
Finally, two-hybrid is a poor choice among poor choices for drug discovery work given that administration of the drug is at the cellular level, not specific to any given interaction.
I've been working on this problem for decades and will be publishing a series of invited papers later this spring in the journal 4Open. Five of those hinge around successful early-stage drug screening that explicitly gauge modulation of protein-protein interactions.
That´s cold water over my wish to test interaction but thank you for the references. I will base my conclusion on the references you cited.
We recently published an empirical approach to developing inhibitors using a library containing protein-protein inhibitors. I guess you might look at this paper and see if it has anything helpful for your thinking. Briefly our chemically diverse, 5000 compound Goldilocks (GL) library has an intermediate number of compounds sized between fragments and drugs with predicted favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological profiles. Amalgamating our core GL library with an approved drug (AD) library, we employ a combined GLAD library virtual screen, enabling an effective and efficient design cycle of ranked computer docking, top hit biophysical and cell validations, and defined bound structures using human proteins or their avatars.
- See Davide Moiani et al., and John A Tainer, Methods Enzymol 2021;661:407-431. An efficient chemical screening method for structure-based inhibitors to nucleic acid enzymes targeting the DNA repair-replication interface and SARS CoV-2
- PMID: 34776222
- PMCID: PMC8474023
- DOI: 10.1016/bs.mie.2021.09.003
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