Dynamical structural correlationsare essential for proteins to realize allostery. Based on analysis of extensive molecular dynamics (MD) simulation trajectories of eleven proteins with different sizes and folds, we found that significant spatially long-range backbone torsional pair correlations exist extensively in some proteins and are dominantly executed by loop residues . Further examinations suggest that such correlations are inherently non-linear and are associated with aharmonic torsional state transitions . Correspondingly, they occur on widely different and relatively longer time scales. In contrast, pair correlations between backbone torsions in stable \alpha helices and \beta strands are dominantly short-ranged, inherently linear, and are associated mainly with harmonic torsional dynamics. Challenges and implications inspired by these observations are discussed .
Protein allostery requires dynamical structural correlations. Physical origin of which, however, remain elusive despite intensive studies during last two decades. Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are spatially more long-ranged and are mainly executed by loop residues , exist extensively in most analyzed proteins. Examination of torsional motion for correlated BTPs suggested that aharmonic torsional state transitions are essential for such non-linear correlations, which correspondingly occur on widely different and relatively longer time scales. In contrast, BTP correlations between backbone torsions in stable \alpha helices and \beta strands are mainly linear and spatially more short-ranged, and are more likely to associate with intra-well torsional dynamics. Further analysis revealed that the direct cause of non-linear contributions are heterogeneous, and in extreme cases canceling, linear correlations associated with different torsional states of participating torsions. Therefore, torsional state transitions of participating torsions for a correlated BTP are only necessary but not sufficient condition for significant non-linear contributions. These findings implicate a general search strategy for novel allosteric modulation of protein activities. Meanwhile, it was suggested that ensemble averaged correlation calculation and static contact network analysis, while insightful, are not sufficient to elucidate mechanisms underlying allosteric signal transmission in general, dynamical and time scale resolved analysis are essential .
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Dynamical structural correlationsare essential for proteins to realize allostery.
Protein allostery requires dynamical structural correlations. Physical origin of which, however, remain elusive despite intensive studies during last two decades.
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Challenges and implications inspired by these observations are discussed
Further analysis revealed that the direct cause of non-linear contributions are heterogeneous, and in extreme cases canceling, linear correlations associated with different torsional states of participating torsions. Therefore, torsional state transitions of participating torsions for a correlated BTP are only necessary but not sufficient condition for significant non-linear contributions. These findings implicate a general search strategy for novel allosteric modulation of protein activities. Meanwhile, it was suggested that ensemble averaged correlation calculation and static contact network analysis, while insightful, are not sufficient to elucidate mechanisms underlying allosteric signal transmission in general, dynamical and time scale resolved analysis are essential