PRISM BioLab Blog – PPI Pursuit

Deep Learning Is Enabling Structure-Based Drug Design: Current Approaches Structure-based drug design (SBDD) or discovery is one of the state-of-art approaches. Computational aid has allowed medicinal chemists to accelerate the drug design in the discovery stages. Now, deep learning (DL) models are enabling the efficient support of SBDD. Emerging DL technologies have potential to lead...

AI/DL technologies provides us a booster for speeding up the drug discovery and development. No one would doubt it in this age of prevalent AI-driven business. However, it is noteworthy that AI/DL often slows down the research. Even though the ability of AI/DL for the acceleration of not only the entire process but also each...

ChatGPT is a well-known large language model (LLM) and is often used in our daily life and business scenes. Its application is expanded from a simple text to a picture and its potential is hard to imagine now. ChatGPT or other LLM could help acceleration of drug discovery and development as well. The issue would...

Do you think it is the age of computer-aided drug discovery (CADD)? The concept of CADD was developed in 1970s Fortune magazine popularized the name.1), 2) It is no doubt that CADD including SBDD and LBDD is raising its value owing to the emergence and sophistication of quantum mechanics, AI-based predictions3) and the intriguing improvement...

Rational and reliable in silico design of a peptide with a high affinity for a specific target protein has been an intense field of research. Natural peptides only possess 20 amino acids and one may imagine that in silico sequence generation would a trivial task with machine learning. However, as the prediction of protein-protein interactions...

Undoubtedly, HTS (high-throughput screening) is a powerful method for library screening.1) Pharmaceutical companies have developed and expanded their original library by internal synthesis and purchase from other institutes. But in a huge real library that quality control and storage cost are annoying issues. It is often the case with library-stored hits that their activity is...

Idealistically speaking, it would be fantastic if drug molecule is readily designed just by the sequence of the target of interest. Structure-based drug design (SBDD) is the currently major approach for drug discovery and development stage. The three-dimensional structure is a key resource even though the advent of AlphaFold2 and RoseTTAFold has offered us beautiful...

How do you think of computer-based prediction of retrosynthesis? Retrosynthesis is a key in synthesis of any molecule without established synthetic routes. When you design a molecule, it is necessary to try retrosynthetic analysis so as to propose a synthetically accessible one. It is frustrating if the designed molecule...

Macrocyclic drug has been intense research field, represented by macrocyclic peptides.¹⁾ It is promising if you see the presence of 67 FDA-approved macrocyclic drugs in 2023. but just over 90 compounds have been reported in approved drugs or those in the clinical stage.²⁾ One of the most examples is the Merck’s phase III case. Merck initiated phase III of MK-0616, an orally available macrocyclic...

Protein-protein interactions (PPIs) library is an indispensable and invaluable tool for PPI drug discovery and development. 2P2Idb v2¹⁾, TIMBAL v2²⁾, iPPI-DB³⁾ have been the libraries focused on PPIs and data availability in the recently elucidated cases were limited for long. It will open up to everyone a great opportunity to initiate another PPIs-targeted drug discovery program if ...