NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois; Biochemistry Center, Heidelberg University, Heidelberg, Germany; Interdisciplinary Center for Scientific Computing, Heidelberg, Germany.
Biochemistry Center, Heidelberg University, Heidelberg, Germany.
Biophys J. 2018 Feb 6;114(3):577-583. doi: 10.1016/j.bpj.2017.12.003.
Molecular dynamics (MD) simulations have become ubiquitous in all areas of life sciences. The size and model complexity of MD simulations are rapidly growing along with increasing computing power and improved algorithms. This growth has led to the production of a large amount of simulation data that need to be filtered for relevant information to address specific biomedical and biochemical questions. One of the most relevant molecular properties that can be investigated by all-atom MD simulations is the time-dependent evolution of the complex noncovalent interaction networks governing such fundamental aspects as molecular recognition, binding strength, and mechanical and structural stability. Extracting, evaluating, and visualizing noncovalent interactions is a key task in the daily work of structural biologists. We have developed PyContact, an easy-to-use, highly flexible, and intuitive graphical user interface-based application, designed to provide a toolkit to investigate biomolecular interactions in MD trajectories. PyContact is designed to facilitate this task by enabling identification of relevant noncovalent interactions in a comprehensible manner. The implementation of PyContact as a standalone application enables rapid analysis and data visualization without any additional programming requirements, and also preserves full in-program customization and extension capabilities for advanced users. The statistical analysis representation is interactively combined with full mapping of the results on the molecular system through the synergistic connection between PyContact and VMD. We showcase the capabilities and scientific significance of PyContact by analyzing and visualizing in great detail the noncovalent interactions underlying the ion permeation pathway of the human P2X receptor. As a second application, we examine the protein-protein interaction network of the mechanically ultrastable cohesin-dockering complex.
分子动力学（MD）模拟已在生命科学的各个领域得到广泛应用。随着计算能力的提高和算法的改进，MD 模拟的规模和模型复杂性正在迅速增长。这一增长导致了大量模拟数据的产生，这些数据需要进行过滤，以提取相关信息，从而解决特定的生物医学和生物化学问题。通过全原子 MD 模拟可以研究的最相关的分子性质之一是控制分子识别、结合强度以及机械和结构稳定性等基本方面的复杂非共价相互作用网络的时间依赖性演化。提取、评估和可视化非共价相互作用是结构生物学家日常工作中的关键任务。我们开发了 PyContact，这是一个易于使用、高度灵活且基于直观图形用户界面的应用程序，旨在提供一个工具包，用于研究 MD 轨迹中的生物分子相互作用。PyContact 的设计目的是通过以可理解的方式识别相关的非共价相互作用来简化此任务。PyContact 作为一个独立的应用程序实现，无需任何额外的编程要求即可实现快速分析和数据可视化，并且还为高级用户保留了完整的程序内自定义和扩展功能。通过 PyContact 与 VMD 的协同连接，将统计分析表示与分子系统上的结果的完全映射以交互方式结合在一起。我们通过详细分析和可视化人类 P2X 受体离子渗透途径的非共价相互作用，展示了 PyContact 的功能和科学意义。作为第二个应用，我们研究了机械超稳定黏着斑蛋白- docking 复合物的蛋白质-蛋白质相互作用网络。
