Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD.
Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bovine pancreatic trypsin inhibitor (BPTI), and the major birch pollen allergen Bet v 1a. We demonstrate excellent agreement of flexibility profiles with both large-scale computer simulations and NMR experiments. Thus, our method provides efficient access to local protein dynamics on extended time scales of high biological relevance.
Institute of General, Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck , Innsbruck, Austria.
Anna S
AS
Kamenik
Institute of General, Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck , Innsbruck, Austria.
Ursula
U
Kahler
Institute of General, Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck , Innsbruck, Austria.
Julian E
JE
Fuchs
Institute of General, Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck , Innsbruck, Austria.
Klaus R
KR
Liedl
D000409:Alanine / Q000737:chemistry; D000818:Animals; D052179:Antigens, Plant / Q000737:chemistry* / Q000378:metabolism; D007611:Aprotinin / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism; D019277:Entropy; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation
D052179:Antigens, Plant; D004151:Dipeptides; D007611:Aprotinin; D000409:Alanine