Pitera Jed W, Swope William
IBM Research, Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA.
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7587-92. doi: 10.1073/pnas.1330954100. Epub 2003 Jun 13.
Replica-exchange molecular dynamics simulations in implicit solvent have been carried out to study the folding thermodynamics of a designed 20-residue peptide, or "miniprotein." The simulations in this study used the amber (parm94) force field along with the generalized Born/solvent-accessible surface area implicit solvent model, and they spanned a range of temperatures from 273 to 630 K. Starting from a completely extended initial conformation, simulations of one peptide sequence sample conformations that are <1.0 A Calpha rms positional deviation from structures in the corresponding NMR ensemble. These folded states are thermodynamically stable with a simulated melting temperature of approximately 400 K, and they satisfy the majority of experimentally observed NMR restraints. Simulations of a related mutant peptide show a degenerate ensemble of states at low temperature, in agreement with experimental results.
已在隐式溶剂中进行复制交换分子动力学模拟，以研究一种设计的20个残基肽（即“微型蛋白质”）的折叠热力学。本研究中的模拟使用了琥珀色（parm94）力场以及广义玻恩/溶剂可及表面积隐式溶剂模型，温度范围为273至630 K。从完全伸展的初始构象开始，对一个肽序列进行模拟，其样本构象与相应NMR系综中的结构相比，Cα位置偏差小于1.0 Å。这些折叠态在热力学上是稳定的，模拟的解链温度约为400 K，并且它们满足大多数实验观察到的NMR约束。对相关突变肽的模拟显示在低温下存在简并态系综，与实验结果一致。
