Harvey S C, Gabb H A
Department of Biochemistry, University of Alabama, School of Medicine, Birmingham 35294.
Biopolymers. 1993 Aug;33(8):1167-72. doi: 10.1002/bip.360330803.
The molecular dynamics algorithm (MD), which simulates intramolecular motions on the subnanosecond timescale, has been modified to allow the investigation of slow conformational transitions that do not necessarily occur spontaneously in MD simulations. The method is designated CONTRA MD (CONformational TRAnsitions by Molecular Dynamics with minimum biasing). The method requires the prior definition of a single conformational variable that is required to vary monotonically from an initial conformation to a final target conformation. The simulation is broken up into a series of short free MD segments, and we determine, after each segment of MD, whether or not the system has evolved toward the final conformation. Those segments that do not move the system in that direction are deleted. Those that do move it toward the final conformation are patched together sequentially to generate a single representative trajectory along the transition pathway. The CONTRA MD method is demonstrated first by application to the simultaneous C2'-endo to C3'-endo repucker and anti to syn N-glycosidic torsion transitions in 2'-deoxyadenosine and then to the large-scale bending in phenylalanine transfer RNA.
分子动力学算法（MD）可在亚纳秒时间尺度上模拟分子内运动，现已进行了改进，以便研究在MD模拟中不一定会自发发生的缓慢构象转变。该方法被命名为CONTRA MD（通过最小偏差分子动力学实现的构象转变）。该方法需要事先定义一个单一的构象变量，该变量需从初始构象到最终目标构象单调变化。模拟被分解为一系列短的自由MD片段，并且在每个MD片段之后，我们确定系统是否已朝着最终构象演化。那些没有使系统朝该方向移动的片段将被删除。那些使系统朝着最终构象移动的片段依次拼接在一起，以生成沿转变途径的单个代表性轨迹。首先通过将CONTRA MD方法应用于2'-脱氧腺苷中同时发生的C2'-内向型到C3'-内向型的核糖重排以及反式到顺式的N-糖苷扭转转变，然后应用于苯丙氨酸转移RNA中的大规模弯曲，对该方法进行了演示。
