Schlitter J, Engels M, Krüger P
Institut für Biophysik, Ruhr-Universität Bochum, Germany.
J Mol Graph. 1994 Jun;12(2):84-9. doi: 10.1016/0263-7855(94)80072-3.
Molecular dynamics simulations have proven to be a valuable tool to investigate the dynamic behavior of stable macromolecules at finite temperatures. However, considerable conformational transitions take place during a simulation only accidentally or at exceptionally high temperatures far from the range of experimental conditions. Targeted molecular dynamics (TMD) is a method to induce a conformational change to a known target structure at ordinary temperature by applying a time-dependent, purely geometrical constraint. The transition is enforced independently of the height of energy barriers, while the dynamics of the molecule is only minimally influenced by the constraint. Simulations of decaalanine and insulin show the ability of the method to explore the configurational space for pathways accessible at a given temperature. The transitions studied at insulin comprise unfolding of an alpha-helical portion and, in the reverse direction, refolding from an extended conformation. A possible application of TMD is the search for energy barriers and stable intermediates from rather local changes up to protein denaturation.
分子动力学模拟已被证明是研究有限温度下稳定大分子动力学行为的一种有价值的工具。然而，在模拟过程中，相当大的构象转变只是偶然发生，或者是在远离实验条件范围的异常高温下发生。靶向分子动力学（TMD）是一种通过应用时间依赖性的纯几何约束，在常温下诱导已知目标结构发生构象变化的方法。这种转变的实现与能垒高度无关，而分子动力学仅受到该约束的最小影响。对十肽丙氨酸和胰岛素的模拟显示了该方法探索给定温度下可及途径的构象空间的能力。在胰岛素上研究的转变包括α-螺旋部分的展开，以及相反方向上从伸展构象的重新折叠。TMD的一个可能应用是从相当局部的变化到蛋白质变性来寻找能垒和稳定中间体。
