- 作者: 林小喬
- 作者服務機構: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, R.O.C.
- 中文摘要: Calculating the configurational entropy associated with conformational fluctuations constitutes an important challenge in modeling macromolecules. Properly estimating configurational entropy is particularly critical for thoroughly understanding protein folding and assessing contending protein folding mechanisms. Here we use tractable systems where the relative configurational entropy can be calculated analytically to assess two such methods: one based on the atom-position covariance-matrix and another based on the cumulative distribution function (CDF) of conformational differences as measured by the root-mean-square difference in atomic coordinates. In cases where the conformational distribution of one state is highly dispersed relative to that of another state, the covariance-matrix greatly overestimates the configurational entropy difference, whereas the CDF reproduces the expected (analytical) difference. As a corollary, the covariance-matrix discounts the majority of entropy loss associated with imposing excluded-chain volume constraints in compact polyalanine conformations with chain lengths corresponding to small proteins (50 to 70 amino acids), compared to CDF-based entropy calculations. The strengths/weakness of the covariance matrix vs. the CDF method for computing relative configurational entropies revealed in this work pave the road to more accurate calculations of the relative configurational entropy of real proteins, in particular upon protein folding.
- 英文摘要: --
- 中文關鍵字: Configurational entropy; Covariance matrix; Cumulative distribution function; Protein folding; Polyalanine.
- 英文關鍵字: --