Experimental Verification of Force Fields for Molecular Dynamics Simulations Using Gly-Pro-Gly-Gly
Experimental Verification of Force Fields for Molecular Dynamics Simulations Using Gly-Pro-Gly-Gly
复制标题
DOI：
10.1021/jp101581h
复制
发表时间：
2010-09-30
影响因子：
3.3
通讯作者：
Courtier-Murias, Denis
中科院分区：
文献类型：
--
作者：
Aliev, Abil E.;Courtier-Murias, Denis
使用12个不同的力场（Amber，Charmm，Gromos和OPLS-AA）对MD模拟进行了实验性NMR验证，并进行了5种不同的水模型，以鉴定可靠的MD协议，以实现包含Gly and Pro的小型开放式链肽的结构和动力学阐明。选择了构象柔性四肽Gly-Pro-Gly-Gly-Gly-gly-NMR（3）J耦合，化学移位和核距离测量值，然后使用2个美国长MD模拟在水中进行计算，此外，Ramachandran人口图用于Ramachandran Maps。从MD模拟获得的GPGG的Pro-2和GLY-3残基用于与蛋白质数据库（PDB）相似地图的详细比较用于蛋白质中的大量gly和Pro残基。 MD模拟揭示了首选主链和侧链构象的种群和几何形状的强烈依赖性，以及肽扭转过渡的时间尺度在使用的力场上。根据对测量和计算的数据的分析，Amber99SB被确定为重现NMR测量参数的最可靠的力场，这些参数取决于肽骨架和Pro侧链几何和动力学。 Ramachandran图显示了使用Amber99SB从MD模拟中gPGG的Pro-2和GLY-3残基的构象种群作为骨架PHI/PSI角的依赖性。发现Amber03和Charmm类似于PDB调查中的Gly和Pro残留物的类似地图。三个力场（Amber99，Amber99 Phi和Amber94）与解决方案NMR和PDB调查数据表现出最不令人满意的一致性。这些力场的性能不佳归因于它们在Pro-2和Gly-3残基处过度稳定的螺旋肽主链构象。根据MD和PDB Ramachandran图的相似性，建议使用以下过渡序列，以实现Gly主链构象：Alpha（L）可逆箭头β（PR）可逆箭头β（S）可逆箭头可逆箭头（P）可逆的可逆箭头beta（P）箭头alpha，骨干二级结构alpha（l）和alpha与螺旋和转弯相关联， β（p）和β（pr）对应于左手和右手的多产II结构，而β（S）表示完全拉伸的骨干构象。与力场依赖性相比，观察到肽主链构象种群的变化较少但值得注意。对于考虑的不同溶剂模型，在使用TIP3P，TIP4P和TIP5P模型时，GPGG中的扭转跃迁数量与水自扩散系数之间存在相关性。除了MD结果外，我们还报告了使用B972和B3LYP功能的GLY和PRO残基的DFT派生的Karplus关系。
Experimental NMR verification of MD simulations using 12 different force fields (AMBER, CHARMM, GROMOS, and OPLS-AA) and 5 different water models has been undertaken to identify reliable MD protocols for structure and dynamics elucidations of small open chain peptides containing Gly and Pro. A conformationally flexible tetrapeptide Gly-Pro-Gly-Gly was selected for NMR (3)J-coupling, chemical shift, and internuclear distance measurements, followed by their calculations using 2 us long MD simulations in water, In addition, Ramachandran population maps for Pro-2 and Gly-3 residues of GPGG obtained from MD simulations were used for detailed comparisons with similar maps from the protein data bank (PDB) for large number of Gly and Pro residues in proteins. The MD simulations revealed strong dependence of the populations and geometries of preferred backbone and side chain conformations, as well as the time scales of the peptide torsional transitions on the force field used. On the basis of the analysis of the measured and calculated data, AMBER99SB is identified as the most reliable force field for reproducing NMR measured parameters, which are dependent on the peptide backbone and the Pro side chain geometries and dynamics. Ramachandran maps showing the dependence of conformational populations as a function of backbone phi/psi angles for Pro-2 and Gly-3 residues of GPGG from MD simulations using AMBER99SB. AMBER03, and CHARMM were found to resemble similar maps for Gly and Pro residues from the PDB survey. Three force fields (AMBER99, AMBER99 phi, and AMBER94) showed the least satisfactory agreement with both the solution NMR and the PDB survey data. The poor performance of these force fields is attributed to their propensity to overstabilize helical peptide backbone conformations at the Pro-2 and Gly-3 residues. On the basis of the similarity of the MD and PDB Ramachandran plots, the following sequence of transitions is suggested for the Gly backbone conformation: alpha(L) reversible arrow beta(pR) reversible arrow beta(s) reversible arrow beta(p) reversible arrow alpha where backbone secondary structures alpha(L), and alpha are associated with helices and turns, beta(P) and beta(PR) correspond to the left- and right-handed polyproline II structures and beta(s) denotes the fully stretched backbone conformation. Compared to the force field dependence, less significant, but noteworthy, variations in the populations of the peptide backbone conformations were observed. For different solvent models considered, a correlation was noted between the number of torsional transitions in GPGG and the water self-diffusion coefficient on using TIP3P, TIP4P, and TIP5P models. In addition to MD results, we also report DFT derived Karplus relationships for Gly and Pro residues using B972 and B3LYP functionals.