Application of the accelerated molecular dynamics simulations to the folding of a small protein.

In this paper, we further explore the applicability of the accelerated molecular dynamics simulation method using a bias potential. The method is applied to both simple model systems and real multidimensional systems. The method is also compared to replica exchange simulations in folding a small protein, Trp cage, using an all atom potential for the protein and an implicit model for the solvent. We show that the bias potential method allows quick searches of folding pathways. We also show that the choice of the bias potential has significant influence on the efficiency of the bias potential method.

[1]  William Swope,et al.  Understanding folding and design: Replica-exchange simulations of ``Trp-cage'' miniproteins , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  D. Case,et al.  Theory and applications of the generalized born solvation model in macromolecular simulations , 2000, Biopolymers.

[3]  W. C. Still,et al.  Semianalytical treatment of solvation for molecular mechanics and dynamics , 1990 .

[4]  D. Hamelberg,et al.  Elasticity of peptide omega bonds. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[5]  Lijiang Yang,et al.  On the enhanced sampling over energy barriers in molecular dynamics simulations. , 2006, The Journal of chemical physics.

[6]  Donald Hamelberg,et al.  Fast peptidyl cis-trans isomerization within the flexible Gly-rich flaps of HIV-1 protease. , 2005, Journal of the American Chemical Society.

[7]  A. Voter.  Hyperdynamics: Accelerated Molecular Dynamics of Infrequent Events , 1997 .

[8]  J. Mongan,et al.  Accelerated molecular dynamics: a promising and efficient simulation method for biomolecules. , 2004, The Journal of chemical physics.

[9]  H. Scheraga,et al.  On the multiple-minima problem in the conformational analysis of molecules: deformation of the potential energy hypersurface by the diffusion equation method , 1989 .

[10]  S. Buldyrev,et al.  Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model. , 2004, Biophysical journal.

[11]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[12]  John W. Wilkins,et al.  Simple bias potential for boosting molecular dynamics with the hyperdynamics scheme , 1998 .

[13]  J. W. Neidigh,et al.  Designing a 20-residue protein , 2002, Nature Structural Biology.

[14]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[15]  Grubmüller,et al.  Predicting slow structural transitions in macromolecular systems: Conformational flooding. , 1995, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[16]  P. Kollman,et al.  How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? , 2000 .

[17]  D. L. Freeman,et al.  Reducing Quasi-Ergodic Behavior in Monte Carlo Simulations by J-Walking: Applications to Atomic Clusters , 1990 .

[18]  A. Laio,et al.  Equilibrium free energies from nonequilibrium metadynamics. , 2006, Physical Review Letters.

[19]  Y. Sugita,et al.  Multidimensional replica-exchange method for free-energy calculations , 2000, cond-mat/0009120.

[20]  B. Berne,et al.  Novel methods of sampling phase space in the simulation of biological systems. , 1997, Current opinion in structural biology.

[21]  Yuko Okamoto,et al.  Theoretical studies of transition states by the multioverlap molecular dynamics methods. , 2006, The Journal of chemical physics.

[22]  J. Tully,et al.  Puddle-skimming: An efficient sampling of multidimensional configuration space , 2002 .

[23]  Y. Sugita,et al.  Replica-exchange molecular dynamics method for protein folding , 1999 .

[24]  C. Tsallis.  Possible generalization of Boltzmann-Gibbs statistics , 1988 .

[25]  Donald Hamelberg,et al.  Phosphorylation effects on cis/trans isomerization and the backbone conformation of serine-proline motifs: accelerated molecular dynamics analysis. , 2005, Journal of the American Chemical Society.

[26]  A. Roitberg,et al.  Smaller and faster: the 20-residue Trp-cage protein folds in 4 micros. , 2002, Journal of the American Chemical Society.

[27]  A. Voter.  A method for accelerating the molecular dynamics simulation of infrequent events , 1997 .

[28]  Shibasish Chowdhury,et al.  Ab initio folding simulation of the Trp-cage mini-protein approaches NMR resolution. , 2003, Journal of molecular biology.

[29]  Martin Karplus,et al.  Probability Distributions for Complex Systems: Adaptive Umbrella Sampling of the Potential Energy , 1998 .

[30]  B. Berg,et al.  Multicanonical algorithms for first order phase transitions , 1991 .

[31]  Donald Hamelberg,et al.  Relating kinetic rates and local energetic roughness by accelerated molecular-dynamics simulations. , 2005, The Journal of chemical physics.

[32]  G. Torrie,et al.  Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling , 1977 .

[33]  A. Roitberg,et al.  All-atom structure prediction and folding simulations of a stable protein. , 2002, Journal of the American Chemical Society.

[34]  V. Pande,et al.  The Trp cage: folding kinetics and unfolded state topology via molecular dynamics simulations. , 2002, Journal of the American Chemical Society.