Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides.: I.: Research design and results on d(CpG) steps
Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides.: I.: Research design and results on d(CpG) steps
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DOI：
10.1529/biophysj.104.045252
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Young, MA
中科院分区：
文献类型：
--
作者：
Beveridge, DL;Barreiro, G;Young, MA
我们在此描述了一个计算密集型项目，旨在对含有所有136个独特四核苷酸碱基序列的B-DNA低聚物进行分子动力学（MD）模拟，包括水和反离子。这项倡议是由九个研究小组，即“阿斯科纳B-DNA联盟”（ABC）的国际合作努力进行的。对嵌入39个具有重复四核苷酸序列的DNA寡聚物的136例进行计算，这些DNA寡聚物两端由GC对盖住，每对总长度为15个核苷酸对。所有的MD模拟都是使用定义良好的协议、AMBER程序套件和parm94力场进行的。ABC项目的第一阶段涉及对包含近24,000个原子的系统进行总计约0.6 μ s的模拟。由此产生的轨迹涉及60万个坐标集，并表示类似400千兆字节的数据。在本文中，描述了研究设计，仿真协议的细节，信息学问题，以及将结果组织到web可访问的数据库中。给出了d（CpG）步骤在其10个独特序列背景下的15-ns MD轨迹的初步结果，并讨论了稳定性和收敛性，拟遍历问题的范围以及长寿命构象亚态的可能性等问题。
We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the "Ascona B-DNA Consortium'' (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of similar to0.6 mus of simulation for systems containing similar to24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent similar to400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed.