Mannige Ranjan V
Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, United States.
Multiscale Institute, Redwood City, CA, United States.
PeerJ. 2017 May 16;5:e3327. doi: 10.7717/peerj.3327. eCollection 2017.
The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom-the backbone dihedral angles and (Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of and has not been completely described for both and backbones. Additionally, little intuitive understanding is available about a peptide's conformation simply from knowing the and values of a peptide (e.g., is the regular peptide defined by = = - 100° left-handed or right-handed?). This report provides a new metric for backbone handedness () based on interpreting a peptide backbone as a helix with axial displacement and angular displacement , both of which are derived from a peptide backbone's internal coordinates, especially dihedral angles , and . In particular, equals sin()∕||, with range [-1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric is used to characterize the handedness of every region of the Ramachandran plot for both ( = 0°) and trans ( = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (, ) space. These maps fill in the 'dead space' within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based on and that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including and backbones. The intuitiveness arises from the fact that and provide, at a glance, numerous aspects of the backbone including compactness, handedness, and planarity.
拉马钱德兰图对结构生物学很重要，因为它在肽主链的主要自由度——主链二面角φ和ψ（拉马钱德兰、拉马克里什南和萨西塞卡兰，1963年）的背景下描述了肽主链。自引入以来，拉马钱德兰图一直是表征蛋白质主链特征的关键工具。然而，对于顺式（φ = 0°）和反式（φ = 180°）主链，主链的构象或扭曲作为φ和ψ的函数尚未得到完整描述。此外，仅仅通过知道肽的φ和ψ值，对于肽的构象几乎没有直观的理解（例如，由φ = ψ = -100°定义的规则肽是左手还是右手？）。本报告基于将肽主链解释为具有轴向位移s和角位移ω的螺旋，提供了一种新的主链手性度量（σ），这两者均源自肽主链的内部坐标，特别是二面角φ、ψ和ω。具体而言，σ等于sin(ω)∕||s||，范围为[-1, 1]，负值（或正值）表示左手性（或右手性）。该度量σ用于表征拉马钱德兰图中顺式（φ = 0°）和反式（φ = 180°）主链每个区域的手性，这首次对拉马钱德兰（φ，ψ）空间中的扭曲手性进行了详尽的调查。这些图谱填补了拉马钱德兰图中的“空白区域”，这些区域是结构化蛋白质通常无法访问的，但可能是内在无序蛋白质、短肽片段和类肽等蛋白质模拟物可以访问的。最后，基于（扎卡里亚斯和克纳普，2013年）的工作，本报告提出了一种基于σ和ω的新图谱，作为拉马钱德兰图的通用且直观的替代方案。这种通用性源于这样一个事实，即这种图谱的共同占据者包括每个可能的肽主链，包括顺式和反式主链。直观性源于这样一个事实，即σ和ω一眼就能提供主链的许多方面，包括紧密性、手性和平坦性。
