皮拉诺斯环过渡状态来自于celllobiohydrolase I诱导的结构稳定性和糖化键极化
Christopher B Barnett1, Karl A Wilkinson, Kevin J Naidoo
1Scientific Computing Research Unit and Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Journal of the American Chemical Society
|August 28, 2010
概括
碳水化合物环球影响药物和材料设计. 新的模拟显示,蛋白质结合稳定了不寻常的葡萄皮酸环形状,驱动了糖化反应.
科学领域:
- 计算化学是一种计算化学.
- 生物物理学的生物物理.
- 碳水化合物的化学成分
背景情况:
- 碳水化合物环器对于材料和药品的合理设计至关重要.
- 精确计算多维自由能源景观是计算上具有挑战性的.
研究的目的:
- 应用新的自适应反应坐标力的自由能量 (FEARCF) 方法来计算多维环的自由能量.
- 在不同环境 (真空,水,蛋白质) 中,研究细胞-寡糖糖体内葡萄糖环的构造偏好.
主要方法:
- 使用自适应反应协调力 (FEARCF) 方法的自由能量.
- 执行了 SCC-DFTB QM/MM 非博尔兹曼模拟.
- 计算的自由能量景观为葡萄皮糖环在细胞-寡糖糖.
主要成果:
- 蛋白质环境显著稳定了 (4) E 和 (4) H (3) 形状,而不是典型的 (4) C (1) 形状.
- 在蛋白质的催化部位内观察到 (4) H ((3) 形状的显著电子重新排列.
- 这些重新排列促进了糖化反应的过渡状态.
结论:
- FEARCF 方法使得能够准确计算多维环形的自由能量.
- 蛋白质结合极大地影响碳水化合物环形状,影响酶活性.
- 了解这些蛋白质诱导的结构变化是设计有效的糖化酶抑制剂和催化剂的关键.
相关概念视频
Stability of Conjugated Dienes
Introduction
A comparison of the enthalpies of hydrogenation of dienes reveals that conjugated dienes release less heat on hydrogenation, rendering them more stable than their nonconjugated analogs.
A comparison of the enthalpies of hydrogenation of dienes reveals that conjugated dienes release less heat on hydrogenation, rendering them more stable than their nonconjugated analogs.
Thermal Electrocyclic Reactions: Stereochemistry
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Chair Conformation of Cyclohexane
The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this staggered...
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this staggered...
Preparation of Diols and Pinacol Rearrangement
Compounds bearing two hydroxyl groups are known as diols. When the hydroxyl groups are located on adjacent carbon atoms, the diols are called vicinal diols or glycols. Under acidic conditions, vicinal diols undergo a specific reaction called pinacol rearrangement.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
Thermal and Photochemical Electrocyclic Reactions: Overview
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.


