A novel approach of dynamic cross correlation analysis on molecular dynamics simulations and its application to Ets1 dimer-DNA complex.
A novel approach of dynamic cross correlation analysis on molecular dynamics simulations and its application to Ets1 dimer-DNA complex.
复制标题
DOI：
10.1371/journal.pone.0112419
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nakamura H
中科院分区：
文献类型：
--
作者：
Kasahara K;Fukuda I;Nakamura H
动态互相关分析是分子动力学模拟中常用的轨迹分析方法。然而，很难检测到仅在轨迹的一部分中瞬时出现的相关运动，例如氨基酸侧链之间的原子接触，其可能快速翻转。为了捕捉这些原子的多模态行为，这往往发挥重要作用，特别是在大分子的界面，我们已经开发了“多模态DCC（mDCC）”分析。mDCC是DCC的扩展，它利用了基于贝叶斯的模式识别技术。我们进行了分子动力学模拟的分子系统建模（Ets 1）2-DNA复合物，并分析了他们的结果与mDCC方法。Ets 1是多种生理过程（如免疫和癌症发展）的必需转录因子。虽然许多结构和生物化学的研究已经进行到目前为止，它的DNA结合性能仍然没有得到很好的表征。特别是，这是不直接理解的分子机制如何合作结合的两个Ets 1分子促进其识别的基质溶素-1基因调控元件。一个相关的网络之间的基本原子的接触，并确定了两个Ets 1分子通信的两个主要途径。一种是通过直接蛋白质-蛋白质相互作用的途径，另一种是通过插入两个识别螺旋的结合DNA的途径。这两种途径在特定的胞嘧啶碱基（C110/C11）上进行，与H1，H2和H3螺旋相互作用。此外，mDCC分析表明，这两种途径包括在其分子间界面的Tyr 396-C11和Ala 327-Asn 380的氨基酸侧链和核苷酸骨架的多模态运动的瞬时相互作用。因此，目前的mDCC方法是一个强大的工具，以揭示这些复杂的行为，并仔细检查分子系统中的分子间通信。
The dynamic cross correlation (DCC) analysis is a popular method for analyzing the trajectories of molecular dynamics (MD) simulations. However, it is difficult to detect correlative motions that appear transiently in only a part of the trajectory, such as atomic contacts between the side-chains of amino acids, which may rapidly flip. In order to capture these multi-modal behaviors of atoms, which often play essential roles, particularly at the interfaces of macromolecules, we have developed the “multi-modal DCC (mDCC)” analysis. The mDCC is an extension of the DCC and it takes advantage of a Bayesian-based pattern recognition technique. We performed MD simulations for molecular systems modeled from the (Ets1)2–DNA complex and analyzed their results with the mDCC method. Ets1 is an essential transcription factor for a variety of physiological processes, such as immunity and cancer development. Although many structural and biochemical studies have so far been performed, its DNA binding properties are still not well characterized. In particular, it is not straightforward to understand the molecular mechanisms how the cooperative binding of two Ets1 molecules facilitates their recognition of Stromelysin-1 gene regulatory elements. A correlation network was constructed among the essential atomic contacts, and the two major pathways by which the two Ets1 molecules communicate were identified. One is a pathway via direct protein-protein interactions and the other is that via the bound DNA intervening two recognition helices. These two pathways intersected at the particular cytosine bases (C110/C11), interacting with the H1, H2, and H3 helices. Furthermore, the mDCC analysis showed that both pathways included the transient interactions at their intermolecular interfaces of Tyr396–C11 and Ala327–Asn380 in multi-modal motions of the amino acid side chains and the nucleotide backbone. Thus, the current mDCC approach is a powerful tool to reveal these complicated behaviors and scrutinize intermolecular communications in a molecular system.
登录
查看更多内容
影响因子：
3.7
作者：
Arakawa T;Kamiya N;Nakamura H;Fukuda I
通讯作者：
Fukuda I
影响因子：
4.8
作者：
Baillat, D;Bègue, A;Aumercier, M
通讯作者：
Aumercier, M
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
11.4
作者：
Kim, WY;Sieweke, M;Ito, Y
通讯作者：
Ito, Y
影响因子：
4.4
作者：
Fukuda, Ikuo;Yonezawa, Yasushige;Nakamura, Haruki
通讯作者：
Nakamura, Haruki