螺旋形成的实验与综合模拟。
Experiments and comprehensive simulations of the formation of a helical turn.
机构信息
Department of Chemistry, Biochemistry, and Institute of Biomedical Studies, Baylor University, Waco, Texas 76706, USA.
出版信息
J Phys Chem B. 2012 Jun 14;116(23):6598-610. doi: 10.1021/jp211645s. Epub 2012 Mar 6.
Abstract
We investigate the kinetics and thermodynamics of a helical turn formation in the peptide Ac-WAAAH-NH(2). NMR measurements indicate that this peptide has significant tendency to form a structure of a helical turn, while temperature dependent CD establishes the helix fraction at different temperatures. Molecular dynamics and milestoning simulations agree with experimental observables and suggest an atomically detailed picture for the turn formation. Using a network representation, two alternative mechanisms of folding are identified: (i) a direct co-operative mechanism from the unfolded to the folded state without intermediate formation of hydrogen bonds and (ii) an indirect mechanism with structural intermediates with two residues in a helical conformation. This picture is consistent with kinetic measurements that reveal two experimental time scales of sub-nanosecond and several nanoseconds.
摘要
我们研究了 Ac-WAAAH-NH(2) 肽中环型结构形成的动力学和热力学。NMR 测量表明，该肽有形成环型结构的强烈趋势，而温度依赖的圆二色性（CD）则在不同温度下确定了螺旋部分的比例。分子动力学和里程碑模拟与实验观测结果一致，并为环形成提供了原子细节的图像。使用网络表示法，确定了两种折叠的替代机制：（i）从无规卷曲到折叠状态的直接协同机制，没有氢键的中间形成，和（ii）具有两个残基处于螺旋构象的结构中间态的间接机制。这种情况与动力学测量一致，该测量揭示了两个实验时间尺度，分别为亚纳秒和几个纳秒。
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