Abstract
Protein dynamics is essential for proteins to function. Here we predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution. These nonlinear excitations arise from the anharmonicity of the protein dynamics. The ILMs were detected by computing the Shannon entropy of the protein main-chain fluctuations. In the non-native state (significantly explored at 380 K), the probability of their excitation was increased by a factor between 9 and 28 for the fast-folder proteins and by a factor 2 for the rigid protein. This enhancement in the non-native state was due to glycine, as demonstrated by simulations in which glycine was mutated to alanine. These ILMs might play a functional role in the flexible regions of proteins and in proteins in a non-native state (i.e. misfolded or unfolded states).
Highlights
Protein dynamics is essential for proteins to function
We predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution
As the loss of rigidity due to the unfolding of a protein increases the anharmonicity of its free-energy landscape, we investigated the dynamics of two ultrafast-folder proteins, Trp-cage[41,42] and the chicken villin headpiece fragment HP-3643,44, above their folding temperature
Summary
We predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution. These nonlinear excitations arise from the anharmonicity of the protein dynamics. We predict a new type of fully classical ILMs in proteins: solitons localized in both time and space ( to the Peregrine solitons[30,31]) These intermittent ILMs are due to the anharmonicity of the potential energy surface describing the torsional degrees of freedom of the main chain of proteins. These coarse-grained angles (CGA) (γ, θ) are part of coarse-grained protein models[37,38] and are used to analyze large conformational changes of proteins and protein folding in all-atom MD simulations[36,39]
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