Chen Zhong, Xu Ying
Dept. of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
J Bioinform Comput Biol. 2006 Apr;4(2):317-33. doi: 10.1142/s0219720006001965.
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 residue and atom levels, respectively. For predictions at the residue level, the helix-helix and helix-membrane interactions were described by a set of knowledge-based energy functions. For predictions at the atom level, CHARMM19 force field was used. To facilitate the system to overcome energy barriers, the Wang-Landau method was employed, where a random walk is performed in the energy space with a uniform probability. Native-like structures were predicted at both levels for two model systems, each of which consists of two transmembrane helices. Interestingly, consistent results were obtained from simulations at the residue and atom levels for the same system, strongly suggesting the feasibility of a hierarchical approach for membrane protein structure predictions.
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-膜相互作用由一组基于知识的能量函数描述。对于原子水平的预测，使用了CHARMM19力场。为了便于系统克服能量障碍，采用了Wang-Landau方法，即在能量空间中以均匀概率进行随机游走。对于两个模型系统（每个系统由两个跨膜螺旋组成），在两个水平上都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得到了一致的结果，这有力地表明了分层方法用于膜蛋白结构预测的可行性。
