TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and 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”和“熵焓补偿”）提出来解释这些能力是不必要的。作为一种催化剂，这些能力是蛋白质结构、性质和动力学中不可或缺的一部分，受到进化的限制和选择。问题是它们是如何起作用的？回答这个问题需要超越当前实验技术的能量和热力学分析，但可以通过计算机模拟。我们的目标是开发一个强大的模拟方法和协议工具包，通过预测一种新酶的机制来盲测它们，并进行后续的实验验证。

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.