Structure-encoded conformational dynamics are crucial for biomolecular functions. However, there is insufficient evidence to support the notion that dynamics play a role in guiding protein-nucleic acid interactions. Here, we show that protein-DNA docking orientation is a function of protein intrinsic dynamics, but the binding site itself does not display unique patterns in the examined spectrum of motions. This revelation is made possible by a novel technique that locates "dynamics interfaces" in proteins across which protein parts are anticorrelated in their slowest dynamics. A striking statistic is that such interfaces intersect the DNA in 97% of the 104 examined cases. These findings were then used to screen decoys generated by rigid-body docking of DNA molecules onto DNA-binding proteins. Using our method, the chance to discern near-native poses from non-native decoys increased by 2.5- and 1.6-fold, as compared to a random guess and methods based on surface complementarity, respectively. Hence, dynamically allowed protein-DNA docking orientations can work as new filters to cull and rerank docking poses and therefore enhance the predictability of DNA-binding sites that themselves do not have distinct dynamics features. Computer software implementing the method can be accessed via http://dyn.life.nthu.edu.tw/IDD/DNA.htm .

No abstract

Life ticks as fast as how efficiently proteins perform their functional dynamics. Wellfolded/structured biomacromolecules perform functions via large-scale intrinsic motions across multiple conformational states, which occur at timescales of nano-to milliseconds.Computationally expensive molecular dynamics (MD) simulation has been the only theoretical tool to gauge the time and sizes of these motions, though barely to their slowest ends. Here, we convert a computationally cheap elastic network model (ENM) into a molecular timer and sizer to gauge the slowest functional motions of proteins and ribosome. Quasi-harmonic analysis, fluctuation-profile matching (FPM) and the Wiener-Khintchine theorem (WKT) are used to define the "time-periods", t, for anharmonic principal components (PCs) which are validated by NMR order parameters. The PCs with their respective "time-periods" are mapped to the eigenvalues (λENM) of the corresponding ENM modes. Thus, the power laws t(ns) = 86.9λENM -1.9 and σ 2 (Å 2 ) = 46.1λENM -2.5 are established allowing the characterization of the time scales of NMR-resolved conformers, crystallographic anisotropic displacement parameters, and important ribosomal motions, as well as motional sizes of the latter. TOC Graphics 4

No abstract

No abstract