Cyclic Peptide Structure Prediction: Potential of AlphaFold Is Expanding

AI and ITs are offering us fabulous opportunities for peptide structure prediction. The impact of AlphaFold2 and RoseTTAFold on protein structure prediction is the typical example that rapidly changes our attitudes on “prediction”. We are also interested because of the expanding potential of computational approaches. AlphaFold is based on a deep learning method and the structural dataset...

Generative de novo Drug Design by an Ensemble of Deep Learning, Cryo-EM and Synthesis

It is no doubt that In silico drug design by structure-based drug design (SBDD) has been a powerful methodology for drug development. Structural data of the target protein, desirably of the binding state with hit or lead compound, delivers us a framework for designing more potent organic molecule structures by medicinal chemists. But with the invent of deep learning, it is realistically...

Deep Learning and Deep Understanding on PPIs Prediction Methods

Computational methods have been paving the way for the advent of PPIs prediction. The emergence and technological development of machine learning raise the possibility of more precise prediction of PPIs. But, for the beginners of machine learning or scientists in other fields, it takes hard time to clearly understand the state-of-the-art computational methods. It often prevents positive attitudes toward predictive methodologies...

Revisit Target-oriented Fragment Linking: SyntaLinker-Hybrid

Now the time to revisit fragment-based drug design (FBDD) in the age of artificial intelligence (AI). The popularity of FBDD has expanded over the past decade owing to the aid of the computational methodology development, the computer spec enhancement and the improved experimental environment. In spite of the world-wide, intensive research by both industry and academia, FBDD has not matured into the crucial breakthrough...

Oral Bioavailability Prediction Screening: Gift of SwissADME

Oral bioavailability is a long-lasting issue on drug development. No one would doubt it as a breakthrough if human oral bioavailability is calculated by the molecule’s chemical structure in high accuracy. Lipinski rule-of-five1) is a rule-of-sum idea to design and choose drug-like molecules with reasonable bioavailability. However, it is not a golden rule and some drugs out-of-criteria are on the market as bioavailable drugs...

PPI Hotspot Targeting: Recent Approaches

Intensive investigation has been conducted in order to rationally identify the “hotspot” of PPI for a decade or even more. In spite of the presence of a myriad of PPI in human, estimated to be 130,0001) to 650,0002) This issue originates from the difficulty in controlling and modulating the PPI of interest by a small molecule. Generally speaking, the contact area of a small molecule inhibitor is thought to be 300 to 1,000 Å2).3)

Conformational Restriction of Peptidomimetics for PPI

Conformational restriction has long been recognized in medicinal chemistry as a rational and effective way for structural design in both drug discovery and optimization stages. This strategy is crucial in PPIs in order for overcoming the energetical inferiority against the original, large-surface-based contact. The exception might be the biomolecule drugs like antibodies which recognized the protein...