月別: 2025年11月

[Published online Journal of Computer Chemistry, Japan Vol.24, 77-79, by J-STAGE]
<Title:> Nonlocal Modulation of Antigen Antibody Interactions Underlying A107R-Mediated Affinity Gain in VHH D2-L29: MD Simulations with MM-PBSA Based Thermodynamic Analysis
<Author(s):> Rika MUNAKATA, Motoki INOUE, Takefumi YAMASHITA
<Corresponding author E-Mill:> yamashita.takefumi(at)hoshi.ac.jp
<Abstract:> Single-domain VHH antibodies offer attractive developability, but rational affinity improvement requires atomistic insight into how sequence changes reshape binding. We investigated the A107R substitution in VHH D2-L29 bound to hen egg-white lysozyme using long-timescale molecular dynamics simulations with MM-PBSA based thermodynamic analysis. Computed binding free energies recapitulated the experimentally observed increase in affinity. Per-residue decomposition of the change in binding free energy indicated that residue 107 (A107R) and Tyr100 had the largest favorable changes, whereas Asn102 had the largest unfavorable change. Together, the results indicate that molecularly detailed, interface-wide analysis of nonlocal interaction changes is essential for rationally engineering VHH variants with enhanced affinity.
<Keywords:> VHH, nanobodies, Molecular dynamics simulations, MM-PBSA, Affinity enhancement
<URL:> https://www.jstage.jst.go.jp/article/jccj/24/3/24_2025-0015/_article/-char/ja/

[Published online Journal of Computer Chemistry, Japan Vol.24, 69-71, by J-STAGE]
<Title:> クロメン誘導体の異性化反応に対する遷移パスサンプリング解析
<Author(s):> 重光　保博, 大賀　恭
<Corresponding author E-Mill:> yshige(at)nagasaki-u.ac.jp
<Abstract:> Chemical reactions with many degrees of freedom are governed by dynamic coupling between fast reaction modes and slow fluctuation ones, particularly in condensed phases. Although this coupling effect is absent when the system maintains chemical equilibrium throughout the reaction, the dynamic effect in solution can be clearly observed under extremely high-pressure conditions where the disparity in intrinsic timescales becomes large enough to disrupt chemical equilibrium between the solute and solvent. In the present study, we computationally investigate the dynamic coupling effect in the ring-closing reaction of chromene (naphtho[2,1-b]pyran), employing a simulation-based approach (Transition Path Sampling: TPS) combined with non-equilibrium reaction theory.
<Keywords:> キーワード Reaction Rate Theory, Non-Equilibrium, Transition Path Sampling, Reaction Coordinate, Committor
<URL:> https://www.jstage.jst.go.jp/article/jccj/24/3/24_2025-0009/_article/-char/ja/

[Published online Journal of Computer Chemistry, Japan Vol.24, 74-76, by J-STAGE]
<Title:> 味覚受容体タンパク質―アミノ酸リガンド複合体における構造変化とゆらぎの分子動力学シミュレーション解析
<Author(s):> 荒木　貴絵, 安藤　耕司
<Corresponding author E-Mill:> ando_k(at)lab.twcu.ac.jp
<Abstract:> Molecular dynamics simulations were performed on the ligand-bound taste receptor proteins T1r2a-T1r3, followed by principal component analysis (PCA). PCA confirmed that ligand binding induces opening and closing motion of the lower part of the protein (the part closer to the cell membrane), with significant movement particularly in T1r3. The free energy landscape revealed features of metastable states reflecting this movement. These results suggest that the movement of T1r3 induced by ligand binding may play an important role in triggering signal transmission to the transmembrane region of the taste receptor.
<Keywords:> Keywords Molecular dynamics simulation, Taste receptor protein, Principal component analysis, Free energy landscape
<URL:> https://www.jstage.jst.go.jp/article/jccj/24/3/24_2025-0012/_article/-char/ja/

[Published online Journal of Computer Chemistry, Japan Vol.24, 72-73, by J-STAGE]
<Title:> PIMD法によるBiuretおよびBiguanideの分子内水素結合構造に対する原子核量子効果の解析
<Author(s):> 西川　琴美, 田中　輝, 桑畑　和明, 立川　仁典, 宇田川　太郎
<Corresponding author E-Mill:> udagawa.taro.f1(at)f.gifu-u.ac.jp
<Abstract:> We focus on the specific features of biuret and biguanide, which adopt a six-membered ring structure via intramolecular hydrogen bonds. The proton donor and acceptor atoms differ between the two molecules, leading to distinct energy barrier heights for proton transfer. To investigate the relationship between proton transfer and the π-electron delocalization within the six-membered ring framework, we performed path integral molecular dynamics (PIMD) simulations. The results show that the π-electrons in the framework are delocalized regardless of the ease of intramolecular proton transfer.
<Keywords:> Keywords Path integral molecular dynamics, Nuclear quantum effects, Intramolecular proton transfer
<URL:> https://www.jstage.jst.go.jp/article/jccj/24/3/24_2025-0011/_article/-char/ja/