Molecular dynamics with the united-residue force field: Ab initio folding simulations of multichain proteins
Molecular dynamics with the united-residue force field: Ab initio folding simulations of multichain proteins
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DOI：
10.1021/jp065810x
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发表时间：
2007-01-11
影响因子：
3.3
通讯作者：
Scheraga, Harold A.
中科院分区：
文献类型：
--
作者：
Rojas, Ana V.;Liwo, Adam;Scheraga, Harold A.
分子动力学联合残基(UNRES)力场的实现被扩展到处理多链蛋白质。在使用Berendsen或Langevin恒温器的模拟中，温度保持恒定。该方法在三个α-螺旋蛋白(1G6U和Gcn4-p1，每个有两个链，1C94，有四个链)上进行了测试。对孤立的单链和多链络合物进行了模拟。蛋白质以随机的初始速度从延伸的构象开始折叠，链相互平行。对于单链或多链络合物，不包含对称性约束或结构信息。在单链模拟的情况下，很高百分比的轨迹(1G6U为100%，GCN4-p1为90%，1C94为80%)收敛到类自然结构(假定为多链复合体中单体的实验结构)，表明对于本工作中在UNRES力场中研究的蛋白质，链之间的相互作用对于单链的稳定并不关键。在多链模拟的情况下，成功地预测了1G6U和Gcn4-p1络合物的天然结构，但没有预测1C94的天然结构。亚基的结合并不遵循一种独特的机制；观察到单体在结合之前和同时折叠。
The implementation of molecular dynamics with the united-residue (UNRES) force field is extended to treat multichain proteins. Constant temperature was maintained in the simulations with Berendsen or Langevin thermostats. The method was tested on three alpha-helical proteins (1G6U and GCN4-p1, each with two chains, and 1C94, with four chains). Simulations were carried out for both the isolated single chains and the multichain complexes. The proteins were folded by starting from the extended conformation with random initial velocities and with the chains parallel to each other. No symmetry constraints or structure information were included for the single chains or the multichain complexes. In the case of single-chain simulations, a high percentage of the trajectories (100% for 1G6U, 90% for GCN4-p1, and 80% for 1C94) converged to nativelike structures (assumed as the experimental structure of a monomer in the multichain complex), showing that, for the proteins studied in this work with the UNRES force field, the interactions between chains are not critical for stabilization of the individual chains. In the case of multichain simulations, the native structures of the 1G6U and GCN4-p1 complexes, but not that of 1C94, are predicted successfully. The association of the subunits does not follow a unique mechanism; the monomers were observed to fold both before and simultaneously with their association.