Application of a chaperone-based refolding method to two- and three-dimensional off-lattice protein models.

A model of protein-chaperone interaction as a two-phase (unfolding/refolding) iterative annealing mechanism able to promote structural segregation of hydrophobic and hydrophilic monomers and thereby facilitate access to nativelike states has recently been applied successfully to two 22-mers of the Honeycutt and Thirumalai BLN (hydrophobic, hydrophilic, neutral) heteropolymer model. This technique is here applied to a much wider data set: 94 8-mers of the off-lattice protein model originally presented in two dimensions by Stillinger and Head-Gordon, and later extended into three dimensions by Irbäck and Potthast; the model chaperone is shown to be equally successful, and by progressive elaboration of the chaperone model as in the earlier BLN model work, to be utilizing very similar underlying mechanisms. It is demonstrated that on average, contacts with the model chaperone give rise to a consistent movement in structure space in the direction of more nativelike structures; this method of global minimization does not therefore rely fundamentally on random search. Insofar as the responses to the chaperone of the two- and three-dimensional forms of the substrate model do differ, this can be interpreted as reflecting the different handling of hydrophilic monomers in the models-in particular, whether there is active repulsion between these and monomers of hydrophobic character. The chaperone-induced refolding method is also tested on a set of 220 9-mer chains of each version of the substrate model, where it is seen that the two-dimensional model, with its more clearly distinguished roles for the hydrophobic and hydrophilic monomers, shows a more favorable scaling behavior.

[1]  D Gorse,et al.  Global minimization of an off‐lattice potential energy function using a chaperone‐based refolding method , 2001, Biopolymers.

[2]  Chris Sander,et al.  Completeness in structural genomics , 2001, Nature Structural Biology.

[3]  H. Saibil,et al.  Molecular chaperones: containers and surfaces for folding, stabilising or unfolding proteins. , 2000, Current opinion in structural biology.

[4]  Jun Wang,et al.  A computational approach to simplifying the protein folding alphabet , 1999, Nature Structural Biology.

[5]  A. Fersht,et al.  GroEL recognises sequential and non-sequential linear structural motifs compatible with extended beta-strands and alpha-helices. , 1999, Journal of molecular biology.

[6]  Adam Liwo,et al.  An Efficient Deformation-Based Global Optimization Method for Off-Lattice Polymer Chains: Self-Consistent Basin-to-Deformed-Basin Mapping (SCBDBM). Application to United-Residue Polypeptide Chains , 1999 .

[7]  J. Weissman,et al.  Thinking outside the box: new insights into the mechanism of GroEL-mediated protein folding , 1999, Nature Structural Biology.

[8]  D Thirumalai,et al.  Exploring the kinetic requirements for enhancement of protein folding rates in the GroEL cavity. , 1999, Journal of molecular biology.

[9]  F. Hartl,et al.  Principles of protein folding in the cellular environment. , 1999, Current opinion in structural biology.

[10]  P B Sigler,et al.  GroEL/GroES: structure and function of a two-stroke folding machine. , 1998, Journal of structural biology.

[11]  F. Hartl,et al.  The oligomeric structure of GroEL/GroES is required for biologically significant chaperonin function in protein folding , 1998, Nature Structural Biology.

[12]  P. Kollman,et al.  Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. , 1998, Science.

[13]  J. Weissman,et al.  GroEL-GroES-mediated protein folding requires an intact central cavity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W. H. Wong,et al.  Molecular Dynamic Simulation of Chaperonin-Mediated Protein Folding , 1998, Journal of Protein Chemistry.

[15]  A. Horovitz.  Structural aspects of GroEL function. , 1998, Current opinion in structural biology.

[16]  H. Taguchi,et al.  Calorimetric Observation of a GroEL-Protein Binding Reaction with Little Contribution of Hydrophobic Interaction* , 1997, The Journal of Biological Chemistry.

[17]  A. Fersht,et al.  A structural model for GroEL-polypeptide recognition. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E S Huang,et al.  Factors affecting the ability of energy functions to discriminate correct from incorrect folds. , 1997, Journal of molecular biology.

[19]  A. Fersht,et al.  Chaperone activity and structure of monomeric polypeptide binding domains of GroEL. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Peterson,et al.  Identification of amino acid sequences with good folding properties in an off-lattice model , 1996, chem-ph/9605002.

[21]  M. Levitt,et al.  Energy functions that discriminate X-ray and near native folds from well-constructed decoys. , 1996, Journal of molecular biology.

[22]  A. Fersht,et al.  Toward a mechanism for GroEL.GroES chaperone activity: an ATPase-gated and -pulsed folding and annealing cage. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  D Thirumalai,et al.  Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  K A Dill,et al.  A simple model of chaperonin‐mediated protein folding , 1996, Proteins.

[25]  E. Shakhnovich,et al.  Simulations of chaperone-assisted folding. , 1996, Biochemistry.

[26]  C. Peterson,et al.  Evidence for Non-Random Hydrophobicity Structures in Protein Chains , 1995, chem-ph/9512004.

[27]  M Levitt,et al.  Recognizing native folds by the arrangement of hydrophobic and polar residues. , 1995, Journal of molecular biology.

[28]  John E. Straub,et al.  FOLDING MODEL PROTEINS USING KINETIC AND THERMODYNAMIC ANNEALING OF THE CLASSICAL DENSITY DISTRIBUTION , 1995 .

[29]  Head-Gordon,et al.  Collective aspects of protein folding illustrated by a toy model. , 1995, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[30]  A. Fersht,et al.  The folding of GroEL-bound barnase as a model for chaperonin-mediated protein folding. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[31]  F. Potthast,et al.  STUDIES OF AN OFF-LATTICE MODEL FOR PROTEIN FOLDING: SEQUENCE DEPENDENCE AND IMPROVED SAMPLING AT FINITE TEMPERATURE , 1995, chem-ph/9505003.

[32]  K Gulukota,et al.  Statistical mechanics of kinetic proofreading in protein folding in vivo. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Thirumalai,et al.  Minimum energy compact structures of random sequences of heteropolymers. , 1993, Physical review letters.

[34]  Head-Gordon,et al.  Optimal neural networks for protein-structure prediction. , 1993, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[35]  J T Ngo,et al.  Computational complexity of a problem in molecular structure prediction. , 1992, Protein engineering.

[36]  D Thirumalai,et al.  The nature of folded states of globular proteins , 1992, Biopolymers.

[37]  K. Dill,et al.  Inverse protein folding problem: designing polymer sequences. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[38]  K. Dill.  Dominant forces in protein folding. , 1990, Biochemistry.

[39]  W. Lim,et al.  Deciphering the message in protein sequences: tolerance to amino acid substitutions. , 1990, Science.

[40]  K. Dill,et al.  A lattice statistical mechanics model of the conformational and sequence spaces of proteins , 1989 .

[41]  W. Lim,et al.  Alternative packing arrangements in the hydrophobic core of λrepresser , 1989, Nature.

[42]  R. Sauer,et al.  Combinatorial cassette mutagenesis as a probe of the informational content of protein sequences. , 1988, Science.

[43]  A. Lesk,et al.  Determinants of a protein fold. Unique features of the globin amino acid sequences. , 1987, Journal of molecular biology.

[44]  D. Eisenberg,et al.  Correlation of sequence hydrophobicities measures similarity in three-dimensional protein structure. , 1983, Journal of molecular biology.

[45]  D. T. Jones.  Critically assessing the state-of-the-art in protein structure prediction , 2001, The Pharmacogenomics Journal.

[46]  Richard Bonneau,et al.  Ab initio protein structure prediction of CASP III targets using ROSETTA , 1999, Proteins.

[47]  Bruce J. Berne,et al.  Global Optimization : Quantum Thermal Annealing with Path Integral Monte Carlo , 1999 .