量子力学/分子力学自由エネルギーシミュレーションによる大豆リポキシゲナーゼにおけるプロトン結合電子移転に関する基本的な洞察
Pengfei Li1,2, Alexander V Soudackov1,2, Sharon Hammes-Schiffer1,2
1Department of Chemistry, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|February 3, 2018
まとめ
大豆のリポキシゲナーゼ
科学分野:
- 生化学と生体物理学
- 酵素学
- コンピュータ化学
背景:
- 陽子結合電子移転 (PCET) 反応は生物系において極めて重要です.
- 大豆リポキシゲナーゼ (SLO) は,PCET反応の原型を触媒化し,酵素による水素トンネリングの理解に不可欠です.
- 野生型 (WT) と二重変異型 (DM) のSLOに対する実験的運動同位体効果 (KIEs) は重要なデータを提供します.
研究 の 目的:
- 先進的な計算シミュレーションを使用して,SLOのPCET反応機構を調査する.
- WT と DM SLO の間での実験的に観察された KIE に寄与する要因を解明する.
- 構造と電子特性と水素トンネルの効率を相関させる.
主な方法:
- 混合量子/古典 (QM/MM) の自由エネルギーシミュレーションが使用されました.
- 自由エネルギー面と平均力 (PMF) のポテンシャルを計算した.
- PCET反応に影響を与えるアンハーモニシティと静電効果を分析した.
主要な成果:
- シミュレーションは,WT (∼80) とDM (∼700) SLOの実験KIEを正確に再現した.
- PCET反応は,WTに対してエクゾエルギックであり,DMに対してわずかにエンドエルギックである.
- 拡張した空洞での基質結合により,DMにおけるより大きな均衡C-O距離は,KIEを大幅に増加させる.
結論:
- DMの拡張された結合腔は,その高いKIEの主要なドライバーです.
- アンハーモニック・ポテンシャルとローカル・エレクトロスタティック・フィールドは 効率的な水素トンネルを容易にする.
- タンパク質環境は基板の調整を助けますが,局所静電はPCETとトンネリングの鍵です.
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