Replica exchange and multicanonical algorithms with the coarse-grained united-residue (UNRES) force field
Replica exchange and multicanonical algorithms with the coarse-grained united-residue (UNRES) force field
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DOI：
10.1021/ct050253o
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发表时间：
2006-05-01
影响因子：
5.5
通讯作者：
Scheraga, Harold A.
中科院分区：
文献类型：
--
作者：
Nanias, Marian;Czaplewski, Cezary;Scheraga, Harold A.
在蒙特卡罗和分子动力学两种版本中，利用粗粒度联合残余电场（UNRES）实现了副本交换法（REM）、副本交换多范式法（REMUCA）和副本交换多范式法（REMUCAREM）三种算法。MD算法使用恒温Berendsen恒温器，具有速度Verlet算法和可变时间步长。该算法应用于一个肽（20个游离末端的丙氨酸残基；ala(20)）和两个小蛋白，即46个残基的α -螺旋蛋白（葡萄球菌蛋白A的B结构域；1BDD）和一个48个残基的α + β蛋白（大肠杆菌Mltd Lysm结构域；1E0G）。计算的热力学平均值，如典型平均能量和热容，在聚l -丙氨酸的所有模拟中都很好地一致，表明算法实现正确，并且所有三种算法对小系统都是同样有效的。对于蛋白质A，所有算法都表现得相当好，尽管在计算结果中观察到一些可变性，而对于更复杂的α + β，蛋白质（1E0G），只有副本交换能够产生可靠的统计数据来计算热力学量。最后，根据交换分子动力学结果，计算了不同温度下的RMSD和旋转半径的自由能图。自由能计算表明聚l -丙氨酸和蛋白A的折叠行为是正确的，而对于1E0G，天然结构只有在很低的温度下才具有最低的自由能。因此，在相同温度下，1E0G的熵贡献大于蛋白A。熵的贡献越大，意味着在给定温度下有更多的可接近的构象，这使得获得有效的构象空间覆盖以获得可靠的热力学性质变得更加困难。在相同的温度下，ala20的熵贡献最小，其次是蛋白A，然后是1E0G。
Three algorithms, namely, a replica exchange method ( REM), a replica exchange multicanonical method (REMUCA), and a replica exchange multicanonical method with replica exchange (REMUCAREM), were implemented with the coarse-grained united-residue force field (UNRES) in both Monte Carlo and molecular dynamics versions. The MD algorithms use the constant-temperature Berendsen thermostat, with the velocity Verlet algorithm and a variable time step. The algorithms were applied to one peptide ( 20 residues of alanine with free ends; ala(20)) and two small proteins, namely, an alpha-helical protein of 46 residues ( the B domain of the staphylococal protein A; 1BDD) and an alpha+beta, protein of 48 residues ( the Escherichia coli Mltd Lysm Domain; 1E0G). Calculated thermodynamic averages, such as canonical average energy and heat capacity, are in good agreement among all simulations for poly-L-alanine, showing that the algorithms were implemented correctly and that all three algorithms are equally effective for small systems. For protein A, all algorithms performed reasonably well, although some variability in the calculated results was observed, whereas for a more complicated alpha+beta, protein ( 1E0G), only replica exchange was capable of producing reliable statistics for calculating thermodynamic quantities. Finally, from the replica exchange molecular dynamics results, we calculated free-energy maps as functions of the RMSD and radius of gyration for different temperatures. The free-energy calculations show correct folding behavior for poly-L-alanine and protein A, while for 1E0G, the native structure had the lowest free energy only at very low temperatures. Hence, the entropy contribution for 1E0G is larger than that for protein A at the same temperature. A larger contribution from entropy means that there are more accessible conformations at a given temperature, making it more difficult to obtain an efficient coverage of conformational space to obtain reliable thermodynamic properties. At the same temperature, ala20 has the smallest entropy contribution, followed by protein A, and then by 1E0G.