A5076104735- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Influenza Virus Research Studies
- Estrogen and related hormone effects
- Synthesis and biological activity
- Free Radicals and Antioxidants
- Crystallography and molecular interactions
- Organic and Molecular Conductors Research
- Quantum and electron transport phenomena
- Advanced Chemical Physics Studies
- Physics of Superconductivity and Magnetism
- Chemical Synthesis and Analysis
- Freezing and Crystallization Processes
- Genomics, phytochemicals, and oxidative stress
- thermodynamics and calorimetric analyses
- Cancer therapeutics and mechanisms
- Arctic and Antarctic ice dynamics
- Bioactive Compounds and Antitumor Agents
- Machine Learning in Materials Science
- Cancer-related gene regulation
RIKEN Center for Biosystems Dynamics Research
2018-2024
Japan Science and Technology Agency
2020-2024
RIKEN
2021
The University of Tokyo
2011-2020
CLS Technology (Norway)
2017
Tokai University
2010-2014
Kobe University
2010
Toho University
2007-2009
Hokkaido University
1992-1997
In this study, the electronic properties of bioactive proteins were analyzed using an ab initio fragment molecular orbital (FMO) methodology in solution: coupling with implicit solvent model based on Poisson–Boltzmann surface area called as FMO-PBSA. We investigated effects practical and heterogeneous targets uneven exposure to solvents unlike deoxyribonucleic acid our recent study. Interfragment interaction energy (IFIE) its decomposition analyses by FMO-PBSA revealed solvent-screening...
We developed the world's first web-based public database for storage, management, and sharing of fragment molecular orbital (FMO) calculation data sets describing complex interactions between biomacromolecules, named FMO Database (https://drugdesign.riken.jp/FMODB/). Each entry in contains relevant background information on how was compiled as well total energy each system interfragment interaction (IFIE) pair decomposition analysis (PIEDA) values. Currently, more than 13 600 sets, a...
Quantum chemical calculations investigated molecular recognition of SARS-CoV-2 spike glycoproteins including its N501Y variant for ACE2 and antibody. Hot spot epitope analyses revealed key residues to design drugs antibodies against COVID-19.
Abstract Several basic leucine zipper (bZIP) transcription factors have accessory motifs in their DNA-binding domains, such as the CNC motif of family or EHR small Maf (sMaf) proteins. proteins heterodimerize with sMaf to recognize CNC–sMaf binding DNA elements (CsMBEs) competition homodimers, but functional role remains elusive. In this study, we report crystal structures Nrf2/NFE2L2, a protein regulating anti-stress transcriptional responses, complex MafG and CsMBE. The restricts...
Abstract Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There an urgent need development of selective and safe reagents mosquito control. Flavonoids, group chemical substances with variable phenolic structures, such as daidzein, have been suggested potential larvicides less risk to environment. However, mode larvicidal action flavonoids has not elucidated. Results Here, we report that several flavonoids, including...
Significant activity changes due to small structural (i.e., cliffs) of serine/threonine kinase Pim1 inhibitors were studied theoretically using the fragment molecular orbital method with mechanics Poisson–Boltzmann surface area (FMO+MM-PBSA) approach. This methodology enables quantum-chemical calculations for large biomolecules solvation. In course drug discovery targeting Pim1, six benzofuranone-class found differ only in position indole-ring nitrogen atom. By comparing various qualities...
We developed an automated FMO calculation protocol (Auto-FMO protocol) to calculate huge numbers of protein and ligand complexes, such as drug discovery targets, by ab initio method. The performs not only calculations but also pre-processing input structures homology modeling missing atoms subsequent MM-based optimization, well post-processing results. In addition, QM/MM optimization complex structures, conformational searches in solvent, MM-PBSA/GBSA can be optionally carried out. this...
Abstract Fragment molecular orbital (FMO) method is a powerful computational tool for structure‐based drug design, in which protein–ligand interactions can be described by the inter‐fragment interaction energy (IFIE) and its pair decomposition analysis (PIEDA). Here, we introduced dynamically averaged (DA) FMO‐based approach dynamics simulations were used to generate multiple complex structures FMO calculations. To assess this approach, examined correlation between experimental binding free...
The spike glycoprotein (S-protein) mediates SARS-CoV-2 entry via intermolecular interaction with human angiotensin-converting enzyme 2. receptor binding domain (RBD) of the S-protein has been considered critical for this and acts as target numerous neutralizing antibodies antiviral peptides. This study used fragment molecular orbital method to analyze interactions between RBD antibodies/peptides extracted crucial residues that can be epitopes. evaluated interfragment energy values 12 showed...
In this study, an ab initio fragment molecular orbital (FMO) methodology was developed to evaluate the solvent effects on electrostatic interactions, which make a significant contribution physical and chemical processes occurring in biological systems. Here, fully polarizable solute consisting of FMO electron density electrostatically coupled with implicit based Poisson–Boltzmann (PB) equation; addition, nonpolar contributions empirically obtained from surface area (SA) were added....
Here, we have constructed neural network-based models that predict atomic partial charges with high accuracy at low computational cost. The were trained using high-quality data acquired from quantum mechanics calculations the fragment molecular orbital method. We succeeded in obtaining highly accurate for three representative systems of proteins, including one large biomolecule (approx. 2000 atoms). novelty our approach is ability to take into account electronic polarization system, which a...
We describe several procedures for the preprocessing of fragment molecular orbital (FMO) calculations on p38 mitogen-activated protein (MAP) kinase and discuss influence protein–ligand interaction energies represented by inter-fragment (IFIEs). The correlation between summation IFIEs a ligand amino acid residues (IFIE-sum) experimental affinity values (IC50) was poor when considered whole set complexes. To improve prediction binding affinity, we carefully classified data charge, DFG-loop...
Lysine-specific demethylase 1 (LSD1/KDM1A) is a promising therapeutic target for the treatment of cancers. Several derivatives tranylcypromine (trans-2-phenylcyclopropylamine) have been developed as LSD1 inhibitors. One such derivative S2157; however, this compound has high hERG channel inhibitory activity and low microsomal stability, making it unsuitable drug candidate. Here, using an in silico inhibition prediction model, we designed, synthesized, evaluated novel series S2157...
trans-2-Phenylcycloproylamine (trans-PCPA) has been used as the scaffold to develop covalent-binding inhibitors against lysine-specific demethylase 1 (LSD1/KDM1A), a therapeutic target for several cancers. However, effects of different structural moieties on inhibitory activity, selectivity, and reactivity these derivatives, including cis isomers, LSD1 its paralogue LSD2/KDM1B are not fully understood. Here we synthesized 65 cis- trans-PCPA derivatives evaluated their activity LSD2. One 7c...
The mechanism to fix helix 12 (H12) in the agonist/antagonist position, which is involved controlling transcriptional activation, of human estrogen receptor α ligand binding domain (hERαLBD) studied by using fragment molecular orbital calculations at Møller-Plesset second-order perturbation levels analyze inter-fragment interaction energies (IFIEs), electrostatic potentials (ESPs), and atomic charges. mutually attractive complementary relationships between H12 highly conserved Lys529/Lys362...