Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton’s equations of motion were used and 3D structural information of known proteins was not required. To evaluate the ability of MD simulationto predict protein structures, we calculated seven short test protein (10–46 residues) in the denatured state and compared their predicted and experimental structures. The predicted structure for Trp-cage (20 residues) was close to the experimental structure by 200-ns MD simulation. For proteins shorter or longer than Trp-cage, root-mean square deviation values were larger than those for Trp-cage. However, secondary structures could be reproduced by MD simulations for proteins with 10–34 residues. Simulations by replica exchange MD were performed, but the results were similar to those from normal MD simulations. These results suggest that normal MD simulations can roughly predict short protein structures and 200-ns simulations are frequently sufficient for estimating the secondary structures of protein (approximately 20 residues). Structural prediction method using only fundamental physical laws are useful for investigating non-natural proteins, such as primitive proteins and artificial proteins for peptide-based drug delivery systems.

A chiral cyclophane-based phosphine efficiently catalyzes the (3 + 2) annulation of allenoate and methyleneindolinones to afford spirooxindoles in high selectivities.

Romidepsin is an anticancer drug that inhibits histone deacetylase (HDAC) in human cells. Recently, we found that romidepsin and its analog, FK-A5, inhibit phosphoinositide 3-kinase. Thus, romidepsin and FK-A5 are expected to be promising HDAC/PI3K dual inhibitors for anticancer therapy. In this study, the HDAC1–inhibitor complex structures were predicted by using computational docking and molecular dynamics (MD) simulations. Because romidepsin and FK-A5 are large cyclic molecules, large numbers of conformers can be obtained for these molecules by computational chemical treatment. The docking poses were extracted by comparing romidepsin and FK-A5 because similar compounds are recognized by proteins in similar binding modes. MD simulations were conducted for the selected docking poses, and the protein–ligand interactions were analyzed. The computational results are expected to be useful for the rational drug design of HDAC inhibitors.

The deamidation rate is relatively high for Asn residues with Phe as the C-terminal adjacent residue in γS-crystallin, which is one of the human crystalline lens proteins. However, peptide-based experiments indicated that bulky amino acid residues on the C-terminal side impaired Asn deamination. In this study, we hypothesized that the side chain of Phe affects the Asn deamidation rate and investigated the succinimide formation process using quantum chemical calculations. The B3LYP density functional theory was used to obtain optimized geometries of energy minima and transition states, and MP2 and M06-2X calculations were used to obtain the single-point energy. Activation barriers and rate-determining step changed depending on the orientation of the Phe side chain. In pathways where an interaction occurred between the benzene ring and the amide group of the Asn residue, the activation barrier was lower than in pathways where this interaction did not occur. Since the aromatic ring is oriented toward the Asn side in experimentally determined structures of γS-crystallin, the above interaction is considered to enhance the Asn deamidation.

1. Existing proteins are composed of only approximately 20 types of amino acids, which are known as Magic 20. However, the reason why only Magic 20 were selected as protein components remains uncle...