TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation

全面描述酶的工作原理：开发模拟方法和协议、盲测预测和实验验证

• 批准号: DP0346292
• 负责人: Prof Jill Gready
• 金额: $ 17.09万
• 依托单位: The Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP0346292
• 关键词: TOWARDS; COMPLETE; DESCRIPTION; HOW; ENZYMES

Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protein, as constrained and selected by evolution. The question is how do they work? Answering this requires energetic and thermodynamic analysis beyond current experimental techniques, but accessible by computer simulation. We aim to develop a robust toolkit of simulation methods and protocols, blind test them by predicting the mechanism of a new enzyme, with followup experimental validation.

酶在温和的生理条件下催化非常奇妙的化学反应。许多特殊的化学概念（如“过渡态稳定化”和“熵-焓补偿”）被提出来解释这些权力是不必要的。对于催化剂来说，这些能力是蛋白质的结构、性质和动力学不可或缺的一部分，受到进化的限制和选择。问题是它们是如何工作的？实现这一点需要超越目前实验技术的能量和热力学分析，但可以通过计算机模拟来实现。我们的目标是开发一个强大的模拟方法和协议工具包，通过预测新酶的机制对其进行盲测，并进行后续实验验证。