An Efficient Null Model for Conformational Fluctuations in Proteins

作者：Harder Tim; Borg Mikael; Bottaro Sandro; Boomsma Wouter; Olsson Simon; Ferkinghoff Borg Jesper; Hamelryck Thomas^*

来源：Structure, 2012, 20(6): 1028-1039.

DOI：10.1016/j.str.2012.03.020

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.

• 出版日期2012-6-6