THOUSAND-GRAIN WEIGHT 6, which is an IAA-glucose hydrolase, preferentially recognizes the structure of the indole ring.

An indole-3-acetic acid (IAA)-glucose hydrolase, THOUSAND-GRAIN WEIGHT 6 (TGW6), negatively regulates the grain weight in rice. TGW6 has been used as a target for breeding increased rice yield. Moreover, the activity of TGW6 has been thought to involve auxin homeostasis, yet the details of this putative TGW6 activity remain unclear.

A new workflow for the effective curation of membrane permeability data from open ADME information.

Membrane permeability is an in vitro parameter that represents the apparent permeability (Papp) of a compound, and is a key absorption, distribution, metabolism, and excretion parameter in drug development. Although the Caco-2 cell lines are the most used cell lines to measure Papp, other cell lines, such as the Madin-Darby Canine Kidney (MDCK), LLC-Pig Kidney 1 (LLC-PK1), and Ralph Russ Canine Kidney (RRCK) cell lines, can also be used to estimate Papp. Therefore, constructing in silico models for Papp estimation using the MDCK, LLC-PK1, and RRCK cell lines requires collecting extensive amounts of in vitro Papp data.

PoSSuM v.3: A Major Expansion of the PoSSuM Database for Finding Similar Binding Sites of Proteins.

Information on structures of protein-ligand complexes, including comparisons of known and putative protein-ligand-binding pockets, is valuable for protein annotation and drug discovery and development. To facilitate biomedical and pharmaceutical research, we developed PoSSuM (https://possum.cbrc.

Applying deep learning to iterative screening of medium-sized molecules for protein-protein interaction-targeted drug discovery.

We combined a library of medium-sized molecules with iterative screening using multiple machine learning algorithms that were ligand-based, which resulted in a large increase of the hit rate against a protein-protein interaction target. This was demonstrated by inhibition assays using a PPI target, Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2), and a deep neural network model based on the first-round assay data showed a highest hit rate of 27.3%.

DLiP-PPI library: An integrated chemical database of small-to-medium-sized molecules targeting protein-protein interactions.

Protein-protein interactions (PPIs) are recognized as important targets in drug discovery. The characteristics of molecules that inhibit PPIs differ from those of small-molecule compounds. We developed a novel chemical library database system (DLiP) to design PPI inhibitors.

Effect of Water Adsorption Layers on the Friction Properties of Fluorinated Amorphous Carbon Films in Ambient Air.

Fluorinated amorphous carbon (a-C:F) films with different microstructures were prepared with bipolar-type plasma-based ion implantation and deposition method by changing the negative bias voltage, and the tribological properties were investigated in ambient air. Their surface chemistry and water adsorption properties were investigated to determine their friction properties. Microstructural analysis results showed that, as the negative bias voltage increased, the density of the films decreased with the promotion of graphitization.

Comprehensive Approach of F Nuclear Magnetic Resonance, Enzymatic, and Methods for Site-Specific Hit Selection and Validation of Fragment Molecules that Inhibit Methionine γ-Lyase Activity.

Fragment-based screening using F NMR (F-FS) is an efficient method for exploring seed and lead compounds for drug discovery. Here, we demonstrate the utility and merits of using F-FS for methionine γ-lyase-binding fragments, together with a F NMR-based competition and mutation assay, as well as enzymatic and methods. F NMR-based assays provided useful information on binding between F-FS hit fragments and target proteins.

Identification of novel inhibitors of Keap1/Nrf2 by a promising method combining protein-protein interaction-oriented library and machine learning.

Protein-protein interactions (PPIs) are prospective but challenging targets for drug discovery, because screening using traditional small-molecule libraries often fails to identify hits. Recently, we developed a PPI-oriented library comprising 12,593 small-to-medium-sized newly synthesized molecules. This study validates a promising combined method using PPI-oriented library and ligand-based virtual screening (LBVS) to discover novel PPI inhibitory compounds for Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2).

Chemical curation to improve data accuracy: recent development of the 3DMET database.

We have developed a three-dimensional structure database of natural metabolites (3DMET). Early development of the 3DMET database relied on content auto-generated from 2D-structures of other chemical databases. From 2009, we began manual curation, obtaining new compounds from published works.