Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains
Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains
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DOI：
10.1073/pnas.0408885102
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发表时间：
2005-02-15
影响因子：
11.1
通讯作者：
Scheraga, HA
中科院分区：
文献类型：
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作者：
Liwo, A;Khalili, M;Scheraga, HA
我们报告应用朗之万动力学的物理为基础的联合剩余（UNRES）力场在我们的实验室开发。在七种蛋白质上运行十个轨迹[PDB ID代码1BDD（α; 46个残基），1GAB（α; 47个残基），1 LQ 7（α; 67个残基），1CLB（α; 75个残基），1 E0 L（β; 28个残基）和11 E0 G（α + β; 48个残基）和1 IGD（alpha+beta; 61残基）]与UNRES力场参数化使用我们最近开发的方法获得的层次结构的能源景观。所有的α-螺旋蛋白质和1 E0 G折叠的天然样结构，而1 IGD和1 E0 L产生了大多数非天然的α-螺旋折叠，虽然天然样结构是最低的能量为这两种蛋白质，这可以归因于忽略熵因子在目前的参数化的UNRES。成功折叠模拟的平均折叠时间为纳秒量级，而即使是超快速折叠的蛋白质也仅在微秒内折叠，这意味着UNRES时间尺度比实验时间尺度大大约三个数量级，因为二级自由度的快速运动被平均掉了。使用单个AMD Athlon MP 2800+处理器，使用Langevin动力学进行折叠平均需要2-10小时的CPU时间，具体取决于蛋白质的大小。由于并行处理的优势，这个过程导致可能性，以探索数以千计的折叠途径，并预测不仅是天然结构，但也折叠方案的蛋白质连同其定量动力学和热力学特征。
We report the application of Langevin dynamics to the physics-based united-residue (UNRES) force field developed in our laboratory. Ten trajectories were run on seven proteins [PDB ID codes 1BDD (alpha; 46 residues), 1GAB (alpha; 47 residues), 1LQ7 (alpha; 67 residues), 1CLB (alpha; 75 residues), 1E0L (beta; 28 residues), and 11E0G (alpha+beta; 48 residues), and 1IGD (alpha+beta; 61 residues)] with the UNRES force field parameterized by using our recently developed method for obtaining a hierarchical structure of the energy landscape. All alpha-helical proteins and 1E0G folded to the native-like structures, whereas 1IGD and 1E0L yielded mostly nonnative alpha-helical folds although the native-like structures are lowest in energy for these two proteins, which can be attributed to neglecting the entropy factor in the current parameterization of UNRES. Average folding times for successful folding simulations were of the order of nanoseconds, whereas even the ultrafast-folding proteins fold only in microseconds, which implies that the UNRES time scale is approximately three orders of magnitude larger than the experimental time scale because the fast motions of the secondary degrees of freedom are averaged out. Folding with Langevin dynamics required 2-10 h of CPU time on average with a single AMD Athlon MP 2800+ processor depending on the size of the protein. With the advantage of parallel processing, this process leads to the possibility to explore thousands of folding pathways and to predict not only the native structure but also the folding scenario of a protein together with its quantitative kinetic and thermodynamic characteristics.