Chipot Christophe, Hénin Jérôme
Equipe de Dynamique des Assemblages Membranaires, UMR CNRS/UHP 7565, Institut Nancéien de Chimie Moléculaire, Université Henri Poincaré, BP 239, 54506 Vandoeuvre-lès-Nancy Cedex, France.
J Chem Phys. 2005 Dec 22;123(24):244906. doi: 10.1063/1.2138694.
The reversible folding of deca-alanine is chosen as a test case for characterizing a method that uses an adaptive biasing force (ABF) to escape from the minima and overcome the barriers of the free-energy landscape. This approach relies on the continuous estimation of a biasing force that yields a Hamiltonian in which no average force is exerted along the ordering parameter xi. Optimizing the parameters that control how the ABF is applied, the method is shown to be extremely effective when a nonequivocal ordering parameter can be defined to explore the folding pathway of the peptide. Starting from a beta-turn motif and restraining xi to a region of the conformational space that extends from the alpha-helical state to an ensemble of extended structures, the ABF scheme is successful in folding the peptide chain into a compact alpha helix. Sampling of this conformation is, however, marginal when the range of xi values embraces arrangements of greater compactness, hence demonstrating the inherent limitations of free-energy methods when ambiguous ordering parameters are utilized.
选择十肽丙氨酸的可逆折叠作为一个测试案例，用于表征一种使用自适应偏置力（ABF）来逃离自由能景观中的最小值并克服障碍的方法。这种方法依赖于对偏置力的连续估计，该偏置力产生一个哈密顿量，其中沿序参量ξ不施加平均力。通过优化控制ABF应用方式的参数，当可以定义一个明确的序参量来探索肽的折叠途径时，该方法被证明极其有效。从一个β-转角基序开始，并将ξ限制在从α-螺旋状态延伸到一组伸展结构的构象空间区域，ABF方案成功地将肽链折叠成一个紧凑的α-螺旋。然而，当ξ值的范围包含更紧凑的排列时，这种构象的采样是有限的，因此证明了在使用模糊序参量时自由能方法的固有局限性。
