Sampling the complex energy landscape of a simple β-hairpin

The folding trajectories of a 16-residue β-hairpin are studied using the activation–relaxation technique with a generic energy model. From more than 70 trajectories, three folding pathways emerge. All involve a simultaneous optimization of the complete hydrophobic and hydrogen bonding interactions. The first two follow closely those observed by previous theoretical studies, while the third can be described as a reptation move of one strand of the β-sheet with respect to the other. This reptation move indicates that non-native interactions can play a dominant role in the folding of secondary structures.

[1]  Barkema,et al.  Event-Based Relaxation of Continuous Disordered Systems. , 1996, Physical review letters.

[2]  M. Billeter,et al.  MOLMOL: a program for display and analysis of macromolecular structures. , 1996, Journal of molecular graphics.

[3]  P. Derreumaux,et al.  Computer simulations aimed at structure prediction of supersecondary motifs in proteins , 2001, Proteins.

[4]  A. Gronenborn,et al.  A novel, highly stable fold of the immunoglobulin binding domain of streptococcal protein G. , 1993, Science.

[5]  L. Serrano,et al.  A short linear peptide that folds into a native stable β-hairpin in aqueous solution , 1994, Nature Structural Biology.

[6]  L. Serrano,et al.  β-hairpin and β-sheet formation in designed linear peptides , 1999 .

[7]  Philippe Derreumaux,et al.  Finding the low-energy forms of avian pancreatic polypeptide with the diffusion-process-controlled Monte Carlo method , 1998 .

[8]  B. Berne,et al.  The free energy landscape for β hairpin folding in explicit water , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  W. F. Gunsteren,et al.  β-Hairpin stability and folding: Molecular dynamics studies of the first β-hairpin of tendamistat , 2000 .

[10]  A Kolinski,et al.  Dynamics and thermodynamics of beta-hairpin assembly: insights from various simulation techniques. , 1999, Biophysical journal.

[11]  Yaoqi Zhou,et al.  Role of hydrophilic and hydrophobic contacts in folding of the second β‐hairpin fragment of protein G: Molecular dynamics simulation studies of an all‐atom model , 2002, Proteins.

[12]  Eric J. Sorin,et al.  β-hairpin folding simulations in atomistic detail using an implicit solvent model1 , 2001 .

[13]  V. Muñoz,et al.  Folding dynamics and mechanism of β-hairpin formation , 1997, Nature.

[14]  N. Mousseau,et al.  Dynamics of lennard-jones clusters: A characterization of the activation-relaxation technique , 2000 .

[15]  J. Dannenberg,et al.  Cooperativity in amide hydrogen bonding chains: implications for protein-folding models. , 2001, Journal of the American Chemical Society.

[16]  M. Karplus,et al.  Understanding beta-hairpin formation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Normand Mousseau,et al.  Exploring the energy landscape of proteins: A characterization of the activation-relaxation technique , 2002 .

[18]  A. Fersht.  On the simulation of protein folding by short time scale molecular dynamics and distributed computing , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Generating ensemble averages for small proteins from extended conformations by Monte Carlo simulations. , 2000, Physical review letters.

[20]  V S Pande,et al.  Molecular dynamics simulations of unfolding and refolding of a beta-hairpin fragment of protein G. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Nohad Gresh,et al.  Many-Body Effects in Systems of Peptide Hydrogen-Bonded Networks and Their Contributions to Ligand Binding: A Comparison of the Performances of DFT and Polarizable Molecular Mechanics , 2000 .

[22]  T Schlick,et al.  The loop opening/closing motion of the enzyme triosephosphate isomerase. , 1998, Biophysical journal.

[23]  Haruki Nakamura,et al.  Conformational transition states of a β‐hairpin peptide between the ordered and disordered conformations in explicit water , 2002, Protein science : a publication of the Protein Society.