蛋白質動力學在蛋白質功能,、酶催化活性和發(fā)病機理等方面起著重要的作用。因此,，人們對計算方法探測蛋白質的構象變化有很大的興趣,。但是分子動力學模擬在計算上代價高，因而被僅限于相對短的時間尺度,。
5月10號,，國際著名期刊Structure在線發(fā)表了哥本哈根大學生物學系生物信息學部等科研機構的一篇題為An Efficient Null Model for Conformational Fluctuations in Proteins的研究論文，介紹了一種用于探索蛋白空間構象的概率統(tǒng)計新方法TYPHON,。
TYPHON是一種用于探索蛋白空間構象的概率統(tǒng)計方法,，它在蛋白局部結構的復雜概率模型和特定的描述非局部相互作用約束裝置的指導下進行。TYPHON用多種復雜的概率統(tǒng)計模型維持蛋白局部結構,，并用簡單的高斯限制維持相關的非局部結構,。
TYPHON能提供蛋白構象改變的信息，這種信息與實驗測量結果一致,。TYPHON為探索蛋白質可能的構象改變提供了一種靈活的,、但計算上有效的方法。(生物谷Bioon.com)
doi:10.1016/j.str.2012.03.020
PMC:
PMID:
An Efficient Null Model for Conformational Fluctuations in Proteins
Tim Harder,，Mikael Borg,，Sandro Bottaro，Wouter Boomsma,，Simon Olsson,，Jesper Ferkinghoff-Borg，Thomas HamelryckSee Affiliations
Summary
Protein dynamics play a crucial role in function,，catalytic activity,，and pathogenesis. Consequently,， there is great interest in computational methods that probe the conformational fluctuations of a protein. However， molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions,， such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic,， but the resulting probabilistic model is well-defined and rigorous. Conceptually， TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible,， yet computationally efficient,， method to explore possible conformational fluctuations in proteins.
