The protein folding problem.

The "protein folding problem" consists of three closely related puzzles: (a) What is the folding code? (b) What is the folding mechanism? (c) Can we predict the native structure of a protein from its amino acid sequence? Once regarded as a grand challenge, protein folding has seen great progress in recent years. Now, foldable proteins and nonbiological polymers are being designed routinely and moving toward successful applications. The structures of small proteins are now often well predicted by computer methods. And, there is now a testable explanation for how a protein can fold so quickly: A protein solves its large global optimization problem as a series of smaller local optimization problems, growing and assembling the native structure from peptide fragments, local structures first.

[1]  L. Pauling,et al.  Atomic coordinates and structure factors for two helical configurations of polypeptide chains. , 1951, Proceedings of the National Academy of Sciences of the United States of America.

[2]  L. Pauling,et al.  The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. , 1951, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Kendrew,et al.  The three-dimensional structure of a protein molecule. , 1961, Scientific American.

[4]  C. Anfinsen,et al.  Side-chain interactions governing the pairing of half-cystine residues in ribonuclease. , 1962, The Journal of biological chemistry.

[5]  H. Scheraga,et al.  Theoretical determination of sterically allowed conformations of a polypeptide chain by a computer method , 1965 .

[6]  P. Flory,et al.  The Role of Dipole Interactions in Determining Polypeptide Configurations , 1965 .

[7]  H A Scheraga,et al.  Minimization of polypeptide energy. I. Preliminary structures of bovine pancreatic ribonuclease S-peptide. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. Anfinsen.  Principles that govern the folding of protein chains. , 1973, Science.

[9]  P. Y. Chou,et al.  Prediction of protein conformation. , 1974, Biochemistry.

[10]  H. Scheraga,et al.  Experimental and theoretical aspects of protein folding. , 1975, Advances in protein chemistry.

[11]  M. Karplus,et al.  Dynamics of folded proteins , 1977, Nature.

[12]  H. Scheraga,et al.  A Method for Predicting Nucleation Sites for Protein Folding Based on Hydrophobic Contacts , 1978 .

[13]  P. Y. Chou,et al.  Empirical predictions of protein conformation. , 1978, Annual review of biochemistry.

[14]  M. Karplus,et al.  Diffusion–collision model for protein folding , 1979 .

[15]  A M Lesk,et al.  Folding units in globular proteins. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[16]  P. S. Kim,et al.  Specific intermediates in the folding reactions of small proteins and the mechanism of protein folding. , 1982, Annual review of biochemistry.

[17]  M. Levitt,et al.  Molecular dynamics of native protein. I. Computer simulation of trajectories. , 1983, Journal of molecular biology.

[18]  A. Fersht,et al.  Hydrogen bonding and biological specificity analysed by protein engineering , 1985, Nature.

[19]  K. Dill.  Theory for the folding and stability of globular proteins. , 1985, Biochemistry.

[20]  A. Lesk,et al.  The relation between the divergence of sequence and structure in proteins. , 1986, The EMBO journal.

[21]  G. Beauchamp.  Background Information , 1987, Journal of learning disabilities.

[22]  P. Wolynes,et al.  Spin glasses and the statistical mechanics of protein folding. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[23]  H. Scheraga,et al.  Monte Carlo-minimization approach to the multiple-minima problem in protein folding. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Goldenberg.  Genetic studies of protein stability and mechanisms of folding. , 1988, Annual review of biophysics and biophysical chemistry.

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

[26]  A. Fersht,et al.  Mapping the transition state and pathway of protein folding by protein engineering , 1989, Nature.

[27]  K. Dill,et al.  Thermal stabilities of globular proteins. , 1989, Biochemistry.

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

[29]  K. Dill,et al.  Origins of structure in globular proteins. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  W. DeGrado,et al.  Design of DNA-binding peptides based on the leucine zipper motif. , 1990, Science.

[31]  J. Richardson,et al.  De novo design, expression, and characterization of Felix: a four-helix bundle protein of native-like sequence. , 1990, Science.

[32]  William F. DeGrado,et al.  De novo design of a Zn2+-binding protein , 1990 .

[33]  M Karplus,et al.  Neural networks for protein structure prediction. , 1991, Methods in enzymology.

[34]  K. Dill,et al.  Folding kinetics of proteins and copolymers , 1992 .

[35]  D. T. Jones,et al.  A new approach to protein fold recognition , 1992, Nature.

[36]  J. Onuchic,et al.  Protein folding funnels: a kinetic approach to the sequence-structure relationship. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Swendsen,et al.  THE weighted histogram analysis method for free‐energy calculations on biomolecules. I. The method , 1992 .

[38]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[39]  R. Unger,et al.  Finding the lowest free energy conformation of a protein is an NP-hard problem: proof and implications. , 1993, Bulletin of mathematical biology.

[40]  K. Dill,et al.  Protein core assembly processes , 1993 .

[41]  Yuko Okamoto,et al.  Prediction of peptide conformation by multicanonical algorithm: New approach to the multiple‐minima problem , 1993, J. Comput. Chem..

[42]  J. Onuchic,et al.  Energy landscapes, glass transitions, and chemical reaction dynamics in biomolecular or solvent environment , 1993 .

[43]  K. Dill,et al.  Cooperativity in protein-folding kinetics. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M Karplus,et al.  Protein folding dynamics: The diffusion‐collision model and experimental data , 1994, Protein science : a publication of the Protein Society.

[45]  G. Rose,et al.  α‐Helix‐forming propensities in peptides and proteins , 1994 .

[46]  K. Dill,et al.  Transition states and folding dynamics of proteins and heteropolymers , 1994 .

[47]  K Fidelis,et al.  A large‐scale experiment to assess protein structure prediction methods , 1995, Proteins.

[48]  C. Dobson.  Finding the right fold , 1995, Nature Structural Biology.

[49]  D. Yee,et al.  Principles of protein folding — A perspective from simple exact models , 1995, Protein science : a publication of the Protein Society.

[50]  A. Fersht,et al.  The structure of the transition state for folding of chymotrypsin inhibitor 2 analysed by protein engineering methods: evidence for a nucleation-condensation mechanism for protein folding. , 1995, Journal of molecular biology.

[51]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[52]  Energetic contribution of side chain hydrogen bonding to the stability of staphylococcal nuclease. , 1995, Biochemistry.

[53]  Z Wang,et al.  Kinetically controlled folding of the serpin plasminogen activator inhibitor 1. , 1996, Biochemistry.

[54]  Luis Serrano,et al.  Different folding transition states may result in the same native structure , 1996, Nature Structural Biology.

[55]  R. Sauer,et al.  Sequence space, folding and protein design. , 1996, Current opinion in structural biology.

[56]  P. S. Kim,et al.  Context-dependent secondary structure formation of a designed protein sequence , 1996, Nature.

[57]  C M Dobson,et al.  Fast and slow tracks in lysozyme folding: insight into the role of domains in the folding process. , 1997, Journal of molecular biology.

[58]  William E. Hart,et al.  Robust Proofs of NP-Hardness for Protein Folding: General Lattices and Energy Potentials , 1997, J. Comput. Biol..

[59]  R. Dyer,et al.  Fast events in protein folding: relaxation dynamics of secondary and tertiary structure in native apomyoglobin. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[60]  S. L. Mayo,et al.  De novo protein design: fully automated sequence selection. , 1997, Science.

[61]  K. Dill,et al.  From Levinthal to pathways to funnels , 1997, Nature Structural Biology.

[62]  A. Fersht.  Nucleation mechanisms in protein folding. , 1997, Current opinion in structural biology.

[63]  Samuel H. Gellman,et al.  Foldamers: A Manifesto , 1998 .

[64]  J. Banavar,et al.  Master Equation Approach to Protein Folding and Kinetic Traps , 1998, cond-mat/9803019.

[65]  D Baker,et al.  The sequences of small proteins are not extensively optimized for rapid folding by natural selection. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Frances H. Arnold,et al.  Molecular evolution by staggered extension process (StEP) in vitro recombination , 1998, Nature Biotechnology.

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

[68]  David A. Agard,et al.  Unfolded conformations of α-lytic protease are more stable than its native state , 1998, Nature.

[69]  D. Baker,et al.  Contact order, transition state placement and the refolding rates of single domain proteins. , 1998, Journal of molecular biology.

[70]  R. Dyer,et al.  Fast events in protein folding: the time evolution of primary processes. , 1998, Annual review of physical chemistry.

[71]  V. Pande,et al.  On the transition coordinate for protein folding , 1998 .

[72]  M Mezei,et al.  Chameleon sequences in the PDB. , 1998, Protein engineering.

[73]  T. Kiefhaber,et al.  The speed limit for protein folding measured by triplet-triplet energy transfer. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[74]  C L Brooks,et al.  Exploring the origins of topological frustration: design of a minimally frustrated model of fragment B of protein A. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[75]  K. Dill.  Polymer principles and protein folding , 1999, Protein science : a publication of the Protein Society.

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

[77]  Folding mechanism of Pseudomonas aeruginosa cytochrome c551: role of electrostatic interactions on the hydrophobic collapse and transition state properties. , 1999, Journal of molecular biology.

[78]  G. Rose,et al.  Is protein folding hierarchic? I. Local structure and peptide folding. , 1999, Trends in biochemical sciences.

[79]  W. Goddard,et al.  The topomer-sampling model of protein folding. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[80]  Flavio Seno,et al.  Protein Structures and Optimal Folding from a Geometrical Variational Principle , 1998, cond-mat/9811246.

[81]  S Doniach,et al.  Characterization of transient intermediates in lysozyme folding with time-resolved small-angle X-ray scattering. , 1999, Journal of molecular biology.

[82]  K A Dill,et al.  Designing polymers that mimic biomolecules. , 1999, Current opinion in structural biology.

[83]  R. A. Goldbeck,et al.  Multiple pathways on a protein-folding energy landscape: kinetic evidence. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Vijay S. Pande,et al.  Screen Savers of the World Unite! , 2000, Science.

[85]  Hierarchical folding of cytochrome c , 2000, Nature Structural Biology.

[86]  J. Udgaonkar,et al.  The slow folding reaction of barstar: the core tryptophan region attains tight packing before substantial secondary and tertiary structure formation and final compaction of the polypeptide chain. , 2000, Journal of molecular biology.

[87]  Michael R. Shirts,et al.  COMPUTING: Screen Savers of the World Unite! , 2000, Science.

[88]  S. Gellman,et al.  Antibiotics: Non-haemolytic β-amino-acid oligomers , 2000, Nature.

[89]  M Cieplak,et al.  Scaling of Folding Properties in Go Models of Proteins , 2000, Journal of biological physics.

[90]  Christian W. Omlin,et al.  Refining hidden Markov models with recurrent neural networks , 2000, Proceedings of the IEEE-INNS-ENNS International Joint Conference on Neural Networks. IJCNN 2000. Neural Computing: New Challenges and Perspectives for the New Millennium.

[91]  R. Nussinov,et al.  Anatomy of protein structures: visualizing how a one-dimensional protein chain folds into a three-dimensional shape. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[92]  J. Onuchic,et al.  Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins. , 2000, Journal of molecular biology.

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

[94]  A. Sali,et al.  Protein Structure Prediction and Structural Genomics , 2001, Science.

[95]  W E Stites,et al.  Packing is a key selection factor in the evolution of protein hydrophobic cores. , 2001, Biochemistry.

[96]  J. Hofrichter,et al.  Effect of Viscosity on the Kinetics of α-Helix and β-Hairpin Formation , 2001 .

[97]  Ivet Bahar,et al.  Transition states and the meaning of Φ-values in protein folding kinetics , 2001, Nature Structural Biology.

[98]  T. Kiefhaber,et al.  Apparent two-state tendamistat folding is a sequential process along a defined route. , 2001, Journal of molecular biology.

[99]  C. Brooks,et al.  From folding theories to folding proteins: a review and assessment of simulation studies of protein folding and unfolding. , 2001, Annual review of physical chemistry.

[100]  L. Mirny,et al.  Protein folding theory: from lattice to all-atom models. , 2001, Annual review of biophysics and biomolecular structure.

[101]  M. Gromiha,et al.  Comparison between long-range interactions and contact order in determining the folding rate of two-state proteins: application of long-range order to folding rate prediction. , 2001, Journal of molecular biology.

[102]  D Baker,et al.  Mechanisms of protein folding. , 2001, Current opinion in structural biology.

[103]  S. Arjunan,et al.  Prediction of Protein Secondary Structure , 2001 .

[104]  B Rost,et al.  EVA: Large‐scale analysis of secondary structure prediction , 2001, Proteins.

[105]  Terrence G. Oas,et al.  Preorganized secondary structure as an important determinant of fast protein folding , 2001, Nature Structural Biology.

[106]  Ajay K. Royyuru,et al.  Blue Gene: A vision for protein science using a petaflop supercomputer , 2001, IBM Syst. J..

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

[108]  S. Marqusee,et al.  Experimental evaluation of topological parameters determining protein-folding rates , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[109]  M. Karplus,et al.  Determination of a transition state at atomic resolution from protein engineering data. , 2002, Journal of molecular biology.

[110]  V. Uversky,et al.  The chicken–egg scenario of protein folding revisited , 2002, FEBS letters.

[111]  Kevin W Plaxco,et al.  How the folding rate constant of simple, single-domain proteins depends on the number of native contacts , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[112]  Antonio Trovato,et al.  Geometry and physics of proteins , 2002, Proteins.

[113]  S. Arjunan,et al.  Protein Secondary Structure Prediction Based on Denoeux Belief Neural Network , 2002 .

[114]  M. Shirts,et al.  Simulation of folding of a small alpha-helical protein in atomistic detail using worldwide-distributed computing. , 2002, Journal of molecular biology.

[115]  S. Englander,et al.  Cytochrome c folding pathway: Kinetic native-state hydrogen exchange , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[116]  W. Eaton,et al.  Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy , 2002, Nature.

[117]  V. Muñoz,et al.  Experimental Identification of Downhill Protein Folding , 2002, Science.

[118]  R. L. Baldwin,et al.  Role of backbone solvation in determining thermodynamic β propensities of the amino acids , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[119]  John Karanicolas,et al.  The origins of asymmetry in the folding transition states of protein L and protein G , 2002, Protein science : a publication of the Protein Society.

[120]  A. Auerbach,et al.  Structure of the transition state of gating in the acetylcholine receptor channel pore: a phi-value analysis. , 2002, Biochemistry.

[121]  V. Muñoz.  Thermodynamics and kinetics of downhill protein folding investigated with a simple statistical mechanical model , 2002 .

[122]  Hongyi Zhou,et al.  Folding rate prediction using total contact distance. , 2002, Biophysical journal.

[123]  R. Srinivasan,et al.  Ab initio prediction of protein structure using LINUS , 2002, Proteins.

[124]  Valerie Daggett,et al.  Unifying features in protein-folding mechanisms , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[125]  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.

[126]  L. Looger,et al.  Computational design of receptor and sensor proteins with novel functions , 2003, Nature.

[127]  H. Wolfson,et al.  Reducing the computational complexity of protein folding via fragment folding and assembly , 2003, Protein science : a publication of the Protein Society.

[128]  R. Zhou.  Free energy landscape of protein folding in water: Explicit vs. implicit solvent , 2003, Proteins.

[129]  Annelise E Barron,et al.  Helical peptoid mimics of lung surfactant protein C. , 2003, Chemistry & biology.

[130]  A. Barron,et al.  Helical peptoid mimics of magainin-2 amide. , 2003, Journal of the American Chemical Society.

[131]  Lei Wang,et al.  Expanding the Genetic Code , 2003, Science.

[132]  Safaai Deris,et al.  Assignment of protein sequence to functional family using neural network & Dempster-Shafer theory , 2003 .

[133]  Ken A Dill,et al.  Folding kinetics of two-state proteins: effect of circularization, permutation, and crosslinks. , 2003, Journal of molecular biology.

[134]  K. Dill,et al.  Folding rates and low-entropy-loss routes of two-state proteins. , 2003, Journal of molecular biology.

[135]  D. Baker,et al.  Design of a Novel Globular Protein Fold with Atomic-Level Accuracy , 2003, Science.

[136]  B. Fierz,et al.  Dynamics of unfolded polypeptide chains as model for the earliest steps in protein folding. , 2003, Journal of molecular biology.

[137]  Kresten Lindorff-Larsen,et al.  Calculation of mutational free energy changes in transition states for protein folding. , 2003, Biophysical journal.

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

[139]  Ceslovas Venclovas,et al.  Assessment of progress over the CASP experiments , 2003, Proteins.

[140]  C. Floudas,et al.  ASTRO-FOLD: a combinatorial and global optimization framework for Ab initio prediction of three-dimensional structures of proteins from the amino acid sequence. , 2003, Biophysical journal.

[141]  T. Kiefhaber,et al.  Origin of unusual phi-values in protein folding: evidence against specific nucleation sites. , 2003, Journal of molecular biology.

[142]  S. Gnanakaran,et al.  Validation of an all-atom protein force field: From dipeptides to larger peptides , 2003 .

[143]  R. Levy,et al.  Free energy surfaces of β‐hairpin and α‐helical peptides generated by replica exchange molecular dynamics with the AGBNP implicit solvent model , 2004 .

[144]  Sheena E Radford,et al.  Switching two-state to three-state kinetics in the helical protein Im9 via the optimisation of stabilising non-native interactions by design. , 2004, Journal of molecular biology.

[145]  Igor B Kuznetsov,et al.  Class‐specific correlations between protein folding rate, structure‐derived, and sequence‐derived descriptors , 2003, Proteins.

[146]  A limiting speed for protein folding at low solvent viscosity. , 2004, Journal of the American Chemical Society.

[147]  Tobin R Sosnick,et al.  Barrier-limited, microsecond folding of a stable protein measured with hydrogen exchange: Implications for downhill folding. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[148]  Yawen Bai,et al.  Structural examination of Φ-value analysis in Protein folding , 2004 .

[149]  A. Fersht,et al.  Phi-value analysis and the nature of protein-folding transition states. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[150]  Modulation of the folding energy landscape of cytochrome C with salt. , 2004, Journal of the American Chemical Society.

[151]  C. Dobson,et al.  Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR , 2004, Nature.

[152]  A. Finkelstein,et al.  Prediction of protein folding rates from the amino acid sequence-predicted secondary structure , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[153]  L. H. Bradley,et al.  De novo proteins from designed combinatorial libraries , 2004, Protein science : a publication of the Protein Society.

[154]  Vijay S Pande,et al.  Using path sampling to build better Markovian state models: predicting the folding rate and mechanism of a tryptophan zipper beta hairpin. , 2004, The Journal of chemical physics.

[155]  Doug Barrick,et al.  An experimentally determined protein folding energy landscape. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[156]  Robin S. Dothager,et al.  Differences in the folding transition state of ubiquitin indicated by φ and ψ analyses , 2004 .

[157]  Ken A Dill,et al.  Cooperativity in two‐state protein folding kinetics , 2003, Protein science : a publication of the Protein Society.

[158]  William Swope,et al.  Describing Protein Folding Kinetics by Molecular Dynamics Simulations. 2. Example Applications to Alanine Dipeptide and a β-Hairpin Peptide† , 2004 .

[159]  Jayant B Udgaonkar,et al.  Increasing stability reduces conformational heterogeneity in a protein folding intermediate ensemble. , 2004, Journal of molecular biology.

[160]  D. Goldenberg,et al.  Alteration of the disulfide‐coupled folding pathway of BPTI by circular permutation , 2004, Protein science : a publication of the Protein Society.

[161]  Alan Grossfield,et al.  Role of solvent in determining conformational preferences of alanine dipeptide in water. , 2004, Journal of the American Chemical Society.

[162]  Yuko Okamoto,et al.  Secondary-structure preferences of force fields for proteins evaluated by generalized-ensemble simulations , 2004 .

[163]  S. Englander,et al.  Hydrogen exchange methods to study protein folding. , 2004, Methods.

[164]  J. Hofrichter,et al.  The protein folding 'speed limit'. , 2004, Current opinion in structural biology.

[165]  J. Kelly,et al.  Toward assessing the position-dependent contributions of backbone hydrogen bonding to beta-sheet folding thermodynamics employing amide-to-ester perturbations. , 2004, Journal of the American Chemical Society.

[166]  V. Muñoz,et al.  Exploring protein-folding ensembles: a variable-barrier model for the analysis of equilibrium unfolding experiments. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[167]  William Swope,et al.  Describing Protein Folding Kinetics by Molecular Dynamics Simulations. 1. Theory , 2004 .

[168]  K. Plaxco,et al.  Experimental investigation of the frequency and substitution dependence of negative phi-values in two-state proteins. , 2005, Biochemistry.

[169]  M. Karplus,et al.  Molecular dynamics and protein function. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[170]  So Much More to Know … , 2005, Science.

[171]  D. Higgins,et al.  Multiple sequence alignments. , 2005, Current opinion in structural biology.

[172]  I. Kevrekidis,et al.  Coarse master equation from Bayesian analysis of replica molecular dynamics simulations. , 2005, The journal of physical chemistry. B.

[173]  Yawen Bai,et al.  A protein folding pathway with multiple folding intermediates at atomic resolution. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[174]  Athi N. Naganathan,et al.  Robustness of downhill folding: guidelines for the analysis of equilibrium folding experiments on small proteins. , 2005, Biochemistry.

[175]  P. Bradley,et al.  Toward High-Resolution de Novo Structure Prediction for Small Proteins , 2005, Science.

[176]  Byoung-Chul Lee,et al.  Folding a nonbiological polymer into a compact multihelical structure. , 2005, Journal of the American Chemical Society.

[177]  A. Liwo,et al.  Physics-based protein-structure prediction using a hierarchical protocol based on the UNRES force field: assessment in two blind tests. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[178]  Vijay S Pande,et al.  Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water. , 2005, The Journal of chemical physics.

[179]  Alena Shmygelska.  Search for folding nuclei in native protein structures , 2005, ISMB.

[180]  Folding time distributions as an approach to protein folding kinetics. , 2005, The journal of physical chemistry. B.

[181]  Kevin W Plaxco,et al.  Protein folding: Defining a “standard” set of experimental conditions and a preliminary kinetic data set of two‐state proteins , 2005, Protein science : a publication of the Protein Society.

[182]  Yang Zhang,et al.  TASSER: An automated method for the prediction of protein tertiary structures in CASP6 , 2005, Proteins.

[183]  A. Fersht,et al.  Ultra-fast barrier-limited folding in the peripheral subunit-binding domain family. , 2005, Journal of molecular biology.

[184]  P. Bolhuis.  Kinetic Pathways of β-Hairpin (Un)folding in Explicit Solvent , 2005 .

[185]  S Walter Englander,et al.  Protein folding: the stepwise assembly of foldon units. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[186]  Thomas R Weikl,et al.  Loop‐closure events during protein folding: Rationalizing the shape of Φ‐value distributions , 2005, Proteins.

[187]  Carlos Bustamante,et al.  Direct Observation of the Three-State Folding of a Single Protein Molecule , 2005, Science.

[188]  Alfonso Valencia,et al.  Assessment of predictions submitted for the CASP6 comparative modeling category , 2005, Proteins.

[189]  V. Pande,et al.  Foldamer dynamics expressed via Markov state models. II. State space decomposition. , 2005, The Journal of chemical physics.

[190]  Valerie Daggett,et al.  Simulation and experiment conspire to reveal cryptic intermediates and a slide from the nucleation-condensation to framework mechanism of folding. , 2005, Journal of molecular biology.

[191]  Charles Seife,et al.  What Is the Universe Made Of? , 2005, Science.

[192]  Shimon Weiss,et al.  Probing structural heterogeneities and fluctuations of nucleic acids and denatured proteins. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[193]  John Moult,et al.  A decade of CASP: progress, bottlenecks and prognosis in protein structure prediction. , 2005, Current opinion in structural biology.

[194]  Marco Punta,et al.  Protein folding rates estimated from contact predictions. , 2005, Journal of molecular biology.

[195]  G. Hummer,et al.  Reaction coordinates and rates from transition paths. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[196]  D. Raleigh,et al.  The protein folding transition state: what are Phi-values really telling us? , 2005, Protein and peptide letters.

[197]  S. Cavagnero,et al.  Role of unfolded state heterogeneity and en‐route ruggedness in protein folding kinetics , 2006, Protein science : a publication of the Protein Society.

[198]  Peter G Wolynes,et al.  P versus Q: structural reaction coordinates capture protein folding on smooth landscapes. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[199]  Fabio Piano,et al.  A peptidomimetic siRNA transfection reagent for highly effective gene silencing. , 2006, Molecular bioSystems.

[200]  J. Hofrichter,et al.  Sub-microsecond protein folding. , 2006, Journal of molecular biology.

[201]  Christine Wurth,et al.  Combinatorial approaches to probe the sequence determinants of protein aggregation and amyloidogenicity. , 2006, Protein and peptide letters.

[202]  Martin Gruebele,et al.  Low barrier kinetics: Dependence on observables and free energy surface , 2006, J. Comput. Chem..

[203]  Victor Muñoz,et al.  Atom-by-atom analysis of global downhill protein folding , 2006, Nature.

[204]  Doug Barrick,et al.  The notch ankyrin domain folds via a discrete, centralized pathway. , 2006, Structure.

[205]  Marc A. Martí-Renom,et al.  MODBASE: a database of annotated comparative protein structure models and associated resources , 2005, Nucleic Acids Res..

[206]  S. Takada,et al.  Shaping up the protein folding funnel by local interaction: lesson from a structure prediction study. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[207]  D. Baker,et al.  Prediction and design of macromolecular structures and interactions , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[208]  Eugene I Shakhnovich,et al.  Identification of the minimal protein-folding nucleus through loop-entropy perturbations. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[209]  A. Fersht,et al.  The transition state for folding of a peripheral subunit-binding domain contains robust and ionic-strength dependent characteristics. , 2006, Journal of Molecular Biology.

[210]  H. Chan,et al.  Criteria for downhill protein folding: Calorimetry, chevron plot, kinetic relaxation, and single‐molecule radius of gyration in chain models with subdued degrees of cooperativity , 2006, Proteins.

[211]  Soonmin Jang,et al.  Direct folding simulation of α‐helices and β‐hairpins based on a single all‐atom force field with an implicit solvation model , 2006 .

[212]  A. Schug,et al.  Basin hopping simulations for all-atom protein folding. , 2006, The Journal of chemical physics.

[213]  Vijay S Pande,et al.  Kinetic definition of protein folding transition state ensembles and reaction coordinates. , 2006, Biophysical journal.

[214]  M. Michael Gromiha,et al.  FOLD-RATE: prediction of protein folding rates from amino acid sequence , 2006, Nucleic Acids Res..

[215]  Samuel H. Gellman,et al.  Rational Development of β-Peptide Inhibitors of Human Cytomegalovirus Entry* , 2006, Journal of Biological Chemistry.

[216]  F. Gai,et al.  Nanosecond Folding Dynamics of a Three-Stranded β-Sheet , 2006 .

[217]  H. Scheraga,et al.  The role of hydrophobic interactions in initiation and propagation of protein folding , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[218]  S Walter Englander,et al.  Order of steps in the cytochrome C folding pathway: evidence for a sequential stabilization mechanism. , 2006, Journal of molecular biology.

[219]  Thomas R Weikl,et al.  Substructural cooperativity and parallel versus sequential events during protein unfolding , 2006, Proteins.

[220]  V. Pande,et al.  Using massively parallel simulation and Markovian models to study protein folding: examining the dynamics of the villin headpiece. , 2006, The Journal of chemical physics.

[221]  Hue Sun Chan,et al.  Conformational entropic barriers in topology-dependent protein folding: perspectives from a simple native-centric polymer model , 2006 .

[222]  Ken A. Dill,et al.  Folding Very Short Peptides Using Molecular Dynamics , 2006, PLoS Comput. Biol..

[223]  R. Doolittle,et al.  Progressive sequence alignment as a prerequisitetto correct phylogenetic trees , 2007, Journal of Molecular Evolution.

[224]  D. W. Bolen,et al.  Anatomy of energetic changes accompanying urea-induced protein denaturation , 2007, Proceedings of the National Academy of Sciences.

[225]  Statistical mechanics of helix bundles using a dynamic programming approach. , 2007, Journal of the American Chemical Society.

[226]  A. Fersht,et al.  Structural Biology: Analysis of 'downhill' protein folding , 2007, Nature.

[227]  Doug Barrick,et al.  Predicting coupling limits from an experimentally determined energy landscape , 2007, Proceedings of the National Academy of Sciences.

[228]  Scott J. Shandler,et al.  Foldamers as versatile frameworks for the design and evolution of function. , 2007, Nature chemical biology.

[229]  K. Dill,et al.  Transition-states in protein folding kinetics: the structural interpretation of Phi values. , 2006, Journal of molecular biology.

[230]  Vijay S Pande,et al.  Protein folding under confinement: A role for solvent , 2007, Proceedings of the National Academy of Sciences.

[231]  M. Oliveberg,et al.  Malleability of protein folding pathways: a simple reason for complex behaviour. , 2007, Current opinion in structural biology.

[232]  Y. Duan,et al.  Two-stage folding of HP-35 from ab initio simulations. , 2007, Journal of molecular biology.

[233]  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.

[234]  L. H. Bradley,et al.  Protein design by binary patterning of polar and nonpolar amino acids. , 1993, Methods in molecular biology.

[235]  S. Marqusee,et al.  Exploring subdomain cooperativity in T4 lysozyme II: Uncovering the C‐terminal subdomain as a hidden intermediate in the kinetic folding pathway , 2007, Protein science : a publication of the Protein Society.

[236]  K. Dill,et al.  Protein folding by zipping and assembly , 2007, Proceedings of the National Academy of Sciences.

[237]  Probe‐dependent and nonexponential relaxation kinetics: Unreliable signatures of downhill protein folding , 2007, Proteins.

[238]  Aravind K. Joshi,et al.  Computational linguistics: A new tool for exploring biopolymer structures and statistical mechanics , 2007 .

[239]  Julia Hockenmaier,et al.  Routes are trees: The parsing perspective on protein folding , 2006, Proteins.

[240]  Richard Wolfenden,et al.  Experimental Measures of Amino Acid Hydrophobicity and the Topology of Transmembrane and Globular Proteins , 2007, The Journal of general physiology.

[241]  S. Lindquist,et al.  A natively unfolded yeast prion monomer adopts an ensemble of collapsed and rapidly fluctuating structures , 2007, Proceedings of the National Academy of Sciences.

[242]  Jeffrey Skolnick,et al.  All-atom ab initio folding of a diverse set of proteins. , 2006, Structure.

[243]  A. Fersht,et al.  Distinguishing between cooperative and unimodal downhill protein folding , 2007, Proceedings of the National Academy of Sciences.

[244]  Vincent A Voelz,et al.  Exploring zipping and assembly as a protein folding principle , 2006, Proteins.

[245]  Jayanth R Banavar,et al.  Physics of proteins. , 2007, Annual review of biophysics and biomolecular structure.

[246]  Y. Duan,et al.  Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations , 2007, Proceedings of the National Academy of Sciences.

[247]  Zbyszek Otwinowski,et al.  Structural genomics: keeping up with expanding knowledge of the protein universe. , 2007, Current opinion in structural biology.

[248]  H. Grubmüller,et al.  Fluctuations of primary ubiquitin folding intermediates in a force clamp. , 2007, Journal of structural biology.

[249]  K. Dill,et al.  The ultimate speed limit to protein folding is conformational searching. , 2007, Journal of the American Chemical Society.

[250]  Jeremy C. Smith,et al.  Hierarchical analysis of conformational dynamics in biomolecules: transition networks of metastable states. , 2007, The Journal of chemical physics.

[251]  Hui Chen,et al.  Secondary structure length as a determinant of folding rate of proteins with two‐ and three‐state kinetics , 2007, Proteins.

[252]  Hongxing Lei,et al.  Ab initio folding of albumin binding domain from all-atom molecular dynamics simulation. , 2007, The journal of physical chemistry. B.

[253]  Juan Liu,et al.  Respective roles of short-and long-range interactions in protein folding , 2004, Wuhan University Journal of Natural Sciences.