Catch bond-like kinetics of helix cracking: network analysis by molecular dynamics and milestoning.

The first events of unfolding of secondary structure under load are considered with Molecular Dynamics simulations and Milestoning analysis of a long helix (126 amino acids). The Mean First Passage Time is a non-monotonic function of the applied load with a maximum of 3.6 ns at about 20 pN. Network analysis of the reaction space illustrates the opening and closing of an off-pathway trap that slows unfolding at intermediate load levels. It is illustrated that the nature of the reaction networks changes as a function of load, demonstrating that the process is far from one-dimensional.

[1]  C. Brooks.  Molecular simulations of peptide and protein unfolding: in quest of a molten globule , 1993 .

[2]  R. Isberg,et al.  Dancing with the Host Flow-Dependent Bacterial Adhesion , 2002, Cell.

[3]  M. Parrinello,et al.  Polymorphic transitions in single crystals: A new molecular dynamics method , 1981 .

[4]  Hoover,et al.  Canonical dynamics: Equilibrium phase-space distributions. , 1985, Physical review. A, General physics.

[5]  Ron Elber,et al.  Revisiting and computing reaction coordinates with Directional Milestoning. , 2011, The journal of physical chemistry. A.

[6]  Robert D Skeel,et al.  Maximum Flux Transition Paths of Conformational Change. , 2009, Journal of chemical theory and computation.

[7]  R. Elber,et al.  Reaction path study of conformational transitions in flexible systems: Applications to peptides , 1990 .

[8]  Multiple barriers in forced rupture of protein complexes. , 2012, The Journal of chemical physics.

[9]  E. Vanden-Eijnden,et al.  Force-clamp analysis techniques give highest rank to stretched exponential unfolding kinetics in ubiquitin. , 2012, Biophysical journal.

[10]  Viola Vogel,et al.  Shear‐dependent ‘stick‐and‐roll’ adhesion of type 1 fimbriated Escherichia coli , 2004, Molecular microbiology.

[11]  A. Berezhkovskii,et al.  Reactive flux and folding pathways in network models of coarse-grained protein dynamics. , 2009, The Journal of chemical physics.

[12]  R. Best,et al.  What is the time scale for α-helix nucleation? , 2011, Journal of the American Chemical Society.

[13]  Berk Hess,et al.  P-LINCS:  A Parallel Linear Constraint Solver for Molecular Simulation. , 2008, Journal of chemical theory and computation.

[14]  Klaus Schulten,et al.  Molecular origin of the hierarchical elasticity of titin: simulation, experiment, and theory. , 2011, Annual review of biophysics.

[15]  Markus J. Buehler,et al.  Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of α-helical and β-sheet protein domains , 2007, Proceedings of the National Academy of Sciences.

[16]  R. Elber,et al.  Unassisted transport of N-acetyl-L-tryptophanamide through membrane: experiment and simulation of kinetics. , 2012, The journal of physical chemistry. B.

[17]  G. Hummer,et al.  Coarse master equations for peptide folding dynamics. , 2008, The journal of physical chemistry. B.

[18]  R. Elber,et al.  Experiments and comprehensive simulations of the formation of a helical turn. , 2012, The journal of physical chemistry. B.

[19]  Charles L. Brooks,et al.  Simulations of peptide conformational dynamics and thermodynamics , 1993 .

[20]  C. Schütte,et al.  Supplementary Information for “ Constructing the Equilibrium Ensemble of Folding Pathways from Short Off-Equilibrium Simulations ” , 2009 .

[21]  Cheng Zhu,et al.  Low Force Decelerates L-selectin Dissociation from P-selectin Glycoprotein Ligand-1 and Endoglycan* , 2004, Journal of Biological Chemistry.

[22]  G. I. Bell.  Models for the specific adhesion of cells to cells. , 1978, Science.

[23]  John D. Morgan,et al.  Diffusion‐controlled reactions: A variational formula for the optimum reaction coordinate , 1983 .

[24]  Ron Elber,et al.  Kinetics of helix unfolding: molecular dynamics simulations with milestoning. , 2009, The journal of physical chemistry. A.

[25]  Ron Elber,et al.  Extending molecular dynamics time scales with milestoning: example of complex kinetics in a solvated peptide. , 2007, The Journal of chemical physics.

[26]  K. Kuczera,et al.  Helix formation in a pentapeptide: experiment and force-field dependent dynamics. , 2010, The journal of physical chemistry. A.

[27]  J. Straub,et al.  The MaxFlux algorithm for calculating variationally optimized reaction paths for conformational transitions in many body systems at finite temperature , 1997 .

[28]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997 .

[29]  K. Konstantopoulos,et al.  Receptor–ligand binding: ‘catch’ bonds finally caught , 2003, Current Biology.

[30]  Eric J. Sorin,et al.  Exploring the helix-coil transition via all-atom equilibrium ensemble simulations. , 2005, Biophysical journal.

[31]  C. Brooks,et al.  Nanosecond time scale folding dynamics of a pentapeptide in water. , 1991, Biochemistry.

[32]  Gerhard Hummer,et al.  Free energy surfaces from single-molecule force spectroscopy. , 2005, Accounts of chemical research.

[33]  Lina M. Nilsson,et al.  A Catch-Bond Based Nanoadhesive Sensitive to Shear Stress , 2004 .

[34]  K. Dill,et al.  Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics. , 2007, The Journal of chemical physics.

[35]  Ron Elber,et al.  Milestoning without a Reaction Coordinate. , 2010, Journal of chemical theory and computation.

[36]  Gerhard Hummer,et al.  Peptide folding kinetics from replica exchange molecular dynamics. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[37]  William H Guilford,et al.  Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Elber,et al.  Early events in helix unfolding under external forces: a milestoning analysis. , 2012, The journal of physical chemistry. B.

[39]  Frank Noé,et al.  Markov state models based on milestoning. , 2011, The Journal of chemical physics.

[40]  G. Hummer,et al.  Helix nucleation kinetics from molecular simulations in explicit solvent , 2001, Proteins.

[41]  O. Dudko,et al.  Locating the barrier for folding of single molecules under an external force. , 2011, Physical review letters.

[42]  G. Hummer,et al.  Conformational diffusion and helix formation kinetics. , 2000, Physical review letters.

[43]  Charles L Brooks,et al.  Protein and peptide folding explored with molecular simulations. , 2002, Accounts of chemical research.

[44]  C. Bustamante,et al.  Direct observation of a force-induced switch in the anisotropic mechanical unfolding pathway of a protein , 2012, Proceedings of the National Academy of Sciences.

[45]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[46]  Viola Vogel,et al.  Catch-bond mechanism of force-enhanced adhesion: counterintuitive, elusive, but ... widespread? , 2008, Cell host & microbe.

[47]  Cheng Zhu,et al.  Catch bonds govern adhesion through L-selectin at threshold shear , 2004, The Journal of cell biology.

[48]  Eric Vanden-Eijnden,et al.  Revisiting the finite temperature string method for the calculation of reaction tubes and free energies. , 2009, The Journal of chemical physics.

[49]  Matthias Rief,et al.  The myosin coiled-coil is a truly elastic protein structure , 2002, Nature materials.

[50]  M. Rief,et al.  Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin , 2011, Proceedings of the National Academy of Sciences.

[51]  Olga Yakovenko,et al.  FimH Forms Catch Bonds That Are Enhanced by Mechanical Force Due to Allosteric Regulation* , 2008, Journal of Biological Chemistry.