TY - JOUR T1 - “Fluctuograms” Reveal the Intermittent Intra-Protein Communication in Subtilisin Carlsberg and Correlate Mechanical Coupling with Co-Evolution A1 - Silvestre-Ryan, Jordi A1 - Lin, Yuchun A1 - Chu, Jhih-Wei Y1 - 2011/03/24 N2 - Author Summary A hallmark of protein molecules is their machine-like behaviors while carrying out biological functions. At the molecular level, molecular signals such as binding a metal ion at an action site can cause long-range effects and alter protein function. Such phenomena are often referred to as intra-protein communication or allosteric coupling. Elucidating the underlying mechanisms could lead to novel discovery of molecular modulators to regulate protein function in a more specific and effective manner. A long-standing puzzle is the roles of the anharmonicity and nonlinearity in protein dynamics. To incorporate these characters in modeling intra-protein communication, we devise a “fluctuogram” analysis to record the choreography of allosteric coupling in an atomic molecular dynamics simulation. We show that fluctuogram analysis can bridge the results of physics-based simulation and sequence alignment in bioinformatics by capturing the residues that exhibit high correlation in a multiple sequence alignment. We also show that the fluctuograms calculated from atomic details have the potential to be applied as a tool to select mutation sites for modulating protein function. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 7 IS - 3 UR - https://doi.org/10.1371/journal.pcbi.1002023 SP - e1002023 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002023 ER -