Chen Zhong, Xu Ying
Dept. of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Proc IEEE Comput Syst Bioinform Conf. 2005:203-7. doi: 10.1109/csb.2005.41.
As the first step toward a multi-scale, hierarchical computational approach for membrane protein structure prediction, the packing of transmembrane helices was modeled at the residual and atomistic levels, respectively. For predictions at the residual level, the helix-helix and helix-lipid interactions were described by a set of knowledge-based energy functions. For predictions at the atomistic level, CHARMM19 force field was employed. To facilitate the system to overcome energy barriers, Wang-Landau sampling was carried out by performing a random walk in the energy and conformational spaces. Native-like structures were predicted at both levels for 2- and 7-helix systems. Interestingly, consistent results were obtained from simulations at residual and atomistic levels for the same system, strongly suggesting the feasibility of a hierarchical approach for membrane structure prediction.
作为迈向用于膜蛋白结构预测的多尺度、分层计算方法的第一步，分别在残基水平和原子水平对跨膜螺旋的堆积进行了建模。对于残基水平的预测，螺旋-螺旋和螺旋-脂质相互作用通过一组基于知识的能量函数来描述。对于原子水平的预测，采用了CHARMM19力场。为了便于系统克服能量障碍，通过在能量和构象空间中进行随机游走开展了Wang-Landau抽样。在残基和原子水平上对2螺旋和7螺旋系统均预测出了类似天然的结构。有趣的是，同一系统在残基和原子水平的模拟中获得了一致的结果，这有力地表明了分层方法用于膜结构预测的可行性。
