The first 10 µs was discarded. Percentages for each cluster along the MD trajectory covering 500 ns were calculated at every time step. where 𝑃(𝑡, 𝑖) and 𝑄(𝑡, 𝑖) represent the probability distributions of data sets 𝑃 and 𝑄 and 𝑖 is the histogram bin index which includes all the data from time 0 to 𝑡 . The last 10 µs of the T-REMD simulation was divided into two 5 µs long trajectories (30-35 µs and 35-40 µs) to assess the convergence of the simulations. In this approach we assumed these two 5 µs long trajectories as two independent simulations. In the process, the covariance matrix was calculated for the 10 µs long trajectory so that each frame was first RMS-fit to an average structure to remove the rotational and translational motions. The eigenvalues and eigenvectors were then obtained for each 5 µs trajectory through diagonalization of the covariance matrix. Consequently, coordinates from each 5 µs trajectory were projected along eigenvectors of choice to obtain the projected values for each given mod. A Gaussian kernel density estimator with 300 bins was utilized to create a histogram for each data set, where Kullback-Leibler divergence at each frame was calculated. The sum over each histogram was then normalized to 1.0 and 600MHz spectrometers equipped with 5-mm triples resonance (TCI) cryogenic probes. 1D and 2D imino (exchangeable) protons were recorded in 5% D2O 95% H2O at 278˚K (5˚C) for unmodified 2×2 GG/GG and 2×2 CC/CC NMR constructs using the 600MHz spectrometer. All other experiments were performed on the 700MHz spectrometer. The m 1 G-labeled samples in H2O were recorded at 283˚K (10˚C). 2D NOESYs for non-exchangeable protons were recorded at 298˚K (25˚C) using a mixing time of 300 ms. Assignments were obtained using standard 2D NOESY, DFQ-COSY, and 1 H- C HSQC Bruker experiments with excitation sculpted water suppression. All spectra were processed and analyzed using TOPSPIN 4.0.6 (Bruker) and visualized using Sparky 3.115 (University of California, San Francisco).