Assessing the effect of conformational averaging on the measured values of observables

被引:58
作者
Bürgi, R [1 ]
Pitera, J [1 ]
van Gunsteren, WF [1 ]
机构
[1] ETH Zurich, Phys Chem Lab, CH-8092 Zurich, Switzerland
关键词
averaging; molecular dynamics; NOE; (3)J-coupling constant; saddle-point approximation;
D O I
10.1023/A:1011295422203
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Experiment and computer simulation are two complementary tools to understand the dynamics and behavior of biopolymers in solution. One particular area of interest is the ensemble of conformations populated by a particular molecule in solution. For example, what fraction of a protein sample exists in its folded conformation? How often does a particular peptide form an alpha helix versus a beta hairpin? To address these questions, it is important to determine the sensitivity of a particular experiment to changes in the distribution of molecular conformations. Consequently, a general analytic formalism is proposed to determine the sensitivity of a spectroscopic observable to the underlying distribution of conformations. A particular strength of the approach is that it provides an expression for a weighted average across conformational substates that is independent of the averaging function used. The formalism is described and applied to experimental and simulated nuclear Overhauser enhancement (NOE) and (3)J-coupling data on peptides in solution.
引用
收藏
页码:305 / 320
页数:16
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