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Our main achievement in 2011 with the support from ACS PRF is the invention of a computational method called the fluctuogram analysis and the application of this method to establish connection between protein conformational dynamics with directed evolution and sequence correlation. This method quantifies the coupling in the network of protein structure during conformational dynamics. The coupling strengths between nodes (protein amino acids) in the network and their temporal evolution are explicitly computed from atomistic molecular dynamics simulations. In analogy to the spectrogram analysis of sound waves, the temporal variation of coupling strengths as a function of time is termed the fluctuogram of protein dynamics. By analyzing and comparing the fluctuograms of Ca2+-bound and apo subtilisin, we illustrate that intermittent conformational changes and the concomitant temporal variation in coupling strengths are important mechanism of allosteric communication in the protein structure network. We have illustrated that the fluctuogram can be used to capture the function-gaining mutation sites of proteins. Furthermore, we show that coupling strengths in the protein structure network exhibit high predictability of protein residues that have high correlation in sequence alignment. Correlation in sequence alignment between protein residues indicates their functional coupling but the origin in physical interactions has been a mystery. The fluctuogram analysis shows that coupling strengths between residues in the structure network can afford the molecular level explanation of sequence correlation. In summary, the support from ACS PRF this year allows us to (a) invent the computational method of the fluctuogram analysis, (b) reveal the intermittent nature of conformational changes and temporal variation in coupling strengths, (b) establish that allosteric coupling can proceed without a drastic change in protein structure, and (c) illustrate that the fluctuogram of protein dynamics can be used to capture function-gaining mutation sites and residues with high correlation in sequence alignment. This work has been published in PloS Computational Biology, which is also reported to the ACS PRF online system. The predictability of protein fluctuogram has been demonstrated repeatedly in several protein systems. Currently, we are applying the fluctuogram analysis to elucidate the effects of solvation in organic solvent on protein dynamics.