TY - JOUR
T1 - Myosin dynamics on the millisecond time scale
AU - Burghardt, Thomas P.
AU - Hu, Jimmy Yan
AU - Ajtai, Katalin
N1 - Funding Information:
This work was supported by the National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin diseases grant R01AR049277 and the Mayo Foundation. We thank Karen Magee and Cristopher Rhea from the Mayo Research Computing Facility for assistance with computing. We gratefully acknowledge comments from an unnamed referee on an earlier version of this manuscript.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/12
Y1 - 2007/12
N2 - Myosin is a motor protein associating with actin and ATP. It translates along actin filaments against a force by transduction of free energy liberated with ATP hydrolysis. Various myosin crystal structures define time points during ATPase showing the protein undergoes large conformation change during transduction over a cycle with ∼ 10 ms periodicity. The protein conformation trajectory between two intermediates in the cycle is surmised by non-equilibrium Monte Carlo simulation utilizing free-energy minimization. The trajectory shows myosin transduction of free energy to mechanical work giving evidence for: (i) a causal relationship between product release and work production in the native isoform that is correctly disrupted in a chemically modified protein, (ii) the molecular basis of ATP-sensitive tryptophan fluorescence enhancement and acrylamide quenching, (iii) an actin-binding site peptide containing the free-energy barrier to ATPase product release defining the rate limiting step and, (iv) a scenario for actin-activation of myosin ATPase.
AB - Myosin is a motor protein associating with actin and ATP. It translates along actin filaments against a force by transduction of free energy liberated with ATP hydrolysis. Various myosin crystal structures define time points during ATPase showing the protein undergoes large conformation change during transduction over a cycle with ∼ 10 ms periodicity. The protein conformation trajectory between two intermediates in the cycle is surmised by non-equilibrium Monte Carlo simulation utilizing free-energy minimization. The trajectory shows myosin transduction of free energy to mechanical work giving evidence for: (i) a causal relationship between product release and work production in the native isoform that is correctly disrupted in a chemically modified protein, (ii) the molecular basis of ATP-sensitive tryptophan fluorescence enhancement and acrylamide quenching, (iii) an actin-binding site peptide containing the free-energy barrier to ATPase product release defining the rate limiting step and, (iv) a scenario for actin-activation of myosin ATPase.
KW - Contractility
KW - Fluorescence quenching mechanism
KW - Free energy minimization
KW - Granger causality
KW - Motor protein structure-function
KW - Non-equilibrium Monte Carlo simulation
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U2 - 10.1016/j.bpc.2007.08.008
DO - 10.1016/j.bpc.2007.08.008
M3 - Article
C2 - 17913331
AN - SCOPUS:35648987097
VL - 131
SP - 15
EP - 28
JO - Biophysical Chemistry
JF - Biophysical Chemistry
SN - 0301-4622
IS - 1-3
ER -