蛋白質幾何結構為其功能與動態基礎原則之研究(I)

Abstract

蛋白質動態與其活性的關聯性， 目前試驗與理論尚無法給於定論。然而此問題對於蛋白質結 構功能動態之了解極為關鍵。目前最計算蛋白質動態最有效的方法，是用分子動力學計算分 子軌跡，但是分子軌跡計算極為費時，限制其有效性。最近我們報導蛋白質幾何結構可直接 導出蛋白質動態1-4，不需計算分子軌跡。這發現使得我們能夠研究大量蛋白質的動態，讓我 們能夠廣泛地研究蛋白質動態在蛋白質蛋白－質蛋白質作用，蛋白質－配體作用，酵素－受 質作用，變構控制。

There is much controversy concerns over whether protein motions can effectively contribute to protein function. At present, neither experimental nor computational results can assertively settle this issue. But to resolve this issue it is vital for a deeper understanding of the protein structure-function-dynamics relationship. At present, the most powerful method to compute protein dynamics is Molecular Dynamics (MD) method. However, MD requires integration of long-time trajectories, which is an extremely time-consuming procedure. This severely limits the effectiveness of MD in the study of the dynamics involving large numbers of proteins. Recently, our group reported1-4 that protein’s atomic fluctuations can be derived directly from its physical geometrical shape without using any mechanical models or sequence information. This surprising finding opens the door for researchers to the possibility of computing protein dynamics for a large collection of proteins, which is never possible before. This allows us to examine in a very extensive way the role of protein dynamics in protein-ligand binding, protein-protein interaction, enzyme-substrate catalysis and allosteric control.