Macromolecular dynamics manifest as disorder in structure determination, which is subsequently accounted for by displacement parameters (also called temperature factors, or B-factors) or alternate conformations. Though B-factors contain detailed information about structural dynamics, they are the total of multiple sources of disorder, making them difficult to interpret and thus little-used in structural analysis. We report here an analytical approach for decomposing molecular disorder into a parsimonious hierarchical series of contributions, providing an intuitive basis for quantitative structural-dynamics analysis. We demonstrate the decomposition of disorder on example SARS-CoV-2 and STEAP4 structures, from both crystallographic and cryo-electron microscopy data, and reveal how understanding of the macromolecular disorder leads to deeper understanding of molecular motions and flexibility, and suggests hypotheses for molecular mechanisms. Here, the authors present a hierarchical disorder model for the analysis of disorder in both crystal and cryo-EM structures. They apply their approach to several structures of three proteins, including SARS-CoV-2 proteins, and discuss mechanistic and dynamical implications.
【저자키워드】 structural biology, Structure determination, 【초록키워드】 Structure, SARS-CoV-2, Cryo-electron microscopy, Proteins, Factors, temperature, molecular, information, Quantitative, cryo-EM structures, Analysis, conformations, structures, Structural analysis, SARS-CoV-2 proteins, Hierarchical, Implications, molecular mechanisms, disorder, parameter, approach, example, accounted, macromolecular, hypothese, STEAP4, 【제목키워드】 disorder, macromolecular,