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Molecular Dynamics Simulations of an Engineered T4 Lysozyme Exclude Helix to Sheet Transition, and Provide Insights into Long Distance, Intra-Protein Switchable Motion.

07:00 EST 8th November 2019 | BioPortfolio

Summary of "Molecular Dynamics Simulations of an Engineered T4 Lysozyme Exclude Helix to Sheet Transition, and Provide Insights into Long Distance, Intra-Protein Switchable Motion."

An engineered variant of T4 Lysozyme serves as a model for studying induced remote conformational changes in a full protein context. The design involves a duplicated surface helix, flanked by two loops, that switches between two different conformations spanning about 20 å. Molecular dynamics simulations of the engineered protein, up to 1 μs, rule out α-helix to β-sheet transitions within the duplicated helix as suggested by others. These simulations highlight how the use of different force fields can lead to radical differences in the structure of the protein. In addition, Markov state modeling and transition path theory were employed to map a 6.6 μs simulation for possible early intermediate states and to provide insights into the onset of the switching motion. The putative intermediates involve the folding of one helical turn in the C-terminal loop through energy driven, sequential rearrangement of nearby salt bridges around the key residue Arg63. These results provide a first step towards understanding the energetics and dynamics of a rather complicated intra-protein motion. This article is protected by copyright. All rights reserved.

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Name: Protein science : a publication of the Protein Society
ISSN: 1469-896X
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Medical and Biotech [MESH] Definitions

A zinc finger motif of approximately 30 amino acids with the general sequence X2-Cys-X2,4-Cys-X12-His-X3,4,5-His that forms a simple beta sheet-beta sheet-alpha helix fold stabilized by zinc ions. It recognizes and binds to a variety of eukaryotic DNA sequences and is very common among sequence-specific DNA BINDING PROTEINS and TRANSCRIPTION FACTORS.

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A computer simulation developed to study the motion of molecules over a period of time.

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A subfamily of HELIX-TURN-HELIX DNA-binding proteins that contain a variable length loop adjacent to the HTH motif. The loop connects two anti-parallel strands and forms a wing when bound to DNA.

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