Osamu Ichihara

TL;DR: A newly developed calorimetric method is employed for comprehensively evaluating the affinity of FAs, sub-Angstrom X-ray crystallography to accurately determine their 3D structure, and energy calculations of the coexisting water molecules using the computer program WaterMap to gain a general understanding of how proteins recognize diverse lipids with different chain lengths.

TL;DR: Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds are investigated.

TL;DR: The results showed that confined polar residues in the large hydrophobic lipid binding pockets of the proteins could be potential targets to modulate the affinity for its ligands.

TL;DR: Assays reveal that the Bz amide-containingCD1d ligands function as NKT cell modulators displaying Th2 cytokine biasing responses, and molecular dynamics simulation studies suggest that the phenyl groups can interact with the aromatic amino acid residues in the lipid binding pocket of CD1d.

TL;DR: In this paper, the authors examined the physical factors that contribute to the change of binding free energy from fragment linking and developed a method to rigorously calculate these different physical contributions, and found that multiple confounding factors make successful fragment linking strategies rare, including possible change of the binding mode of fragments in the linked state compared to separate binding of the fragments, unfavorable intramolecular strain energy of the bioactive conformation of the linked molecule, unfavorable interaction between the linker and the protein, favorable interaction energies between two fragments in solution when not chemically linked that offset the expected entropy loss for