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Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics

By Ronald D. Hills and Charles L. Brooks

Abstract

Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō models, which constitute a smooth and funnel-like approximation to the folding landscape. We review the many variations of the Gō model that have been employed to yield insight into folding mechanisms. Their success has been interpreted as a consequence of the dominant role of the native topology in folding. The role of local contact density in determining protein dynamics is also discussed and is used to explain the ability of Gō-like models to capture sequence effects in folding and elucidate conformational transitions

Topics: Review
Publisher: Molecular Diversity Preservation International (MDPI)
OAI identifier: oai:pubmedcentral.nih.gov:2672008
Provided by: PubMed Central
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    Citations

    1. (2008). A coarse-grained alpha-carbon protein model with anisotropic hydrogen-bonding. Proteins
    2. (2006). A new perspective on response regulator activation.
    3. (1999). A simple model for calculating the kinetics of protein folding from three-dimensional structures.
    4. (2005). A survey of flexible protein binding mechanisms and their transition states using native topology based energy landscapes.
    5. (1995). A test of lattice protein folding algorithms.
    6. (1999). A theoretical search for folding/unfolding nuclei in threedimensional protein structures.
    7. (2007). A tightly packed hydrophobic cluster directs the formation of an off-pathway sub-millisecond folding intermediate in the alpha subunit of tryptophan synthase, a TIM barrel protein.
    8. (2008). Advillin folding takes place on a hypersurface of small dimensionality.
    9. (2009). An all-atom structure-based potential for proteins: Bridging minimal models with all-atom empirical forcefields. Proteins. In press,
    10. (2007). and charged amino acid networks within protein.
    11. (2004). and evolution: Understanding nucleation in protein S6 folding.
    12. (2006). and shape: Guiding principles for robustness in macromolecular machines.
    13. (2005). Balancing energy and entropy: A minimalist model for the characterization of protein folding landscapes.
    14. (2006). Can conformational change be described by only a few normal modes?
    15. (2008). celllike environment induces shape changes in aspherical protein.
    16. (2008). Characterization of protein folding by dominant reaction pathways.
    17. (2005). Chevron Behavior and isostable enthalpic barriers in protein folding: Successes and limitations of simple Go-like modeling.
    18. (2005). Chirality and protein folding.
    19. Clusters of isoleucine, leucine and valine side chains define cores of stability in globular proteins: Sequence determinants of structure, stability and folding. 2009, Pending publication.
    20. (2006). Coarse grained protein-lipid model with application to lipoprotein particles.
    21. (2007). Coarse-grained free energy functions for studying protein conformational changes: A double-well network model.
    22. (2005). Coarse-grained model of proteins incorporating atomistic detail of the active site.
    23. (2005). Coarse-grained models for proteins.
    24. Coarse-grained protein model coupled with a coarse-grained water model: Molecular dynamics study of polyalanine-based peptides.
    25. (2008). Coevolution of function and the folding landscape: Correlation with density of native contacts.
    26. (2001). Conformational change of proteins arising from normal mode calculations. Protein Eng.
    27. (2007). Conformational transitions of adenylate kinase: Switching by cracking.
    28. (2003). Contact order revisited: Influence of protein size on the folding rate. Protein Sci.
    29. (1998). Contact order, transition state placement and the refolding rates of single domain proteins.
    30. (2009). Crowding effects on the mechanical stability and unfolding pathways of ubiquitin.
    31. (2008). Crystallographic B-factors highlight energetic frustration in aldolase folding.
    32. (2007). Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids. Nano Lett.
    33. (1998). Discrete molecular dynamics studies of the folding of a protein-like model.
    34. (2002). Dynamics of large proteins through hierarchical levels of coarse-grained structures.
    35. (2006). Effect of finite size on cooperativity and rates of protein folding.
    36. (2005). Effects of frustration, confinement, and surface interactions on the dimerization of an off-lattice beta-barrel protein.
    37. (2006). Elucidation of conserved long-range interaction networks in proteins and their significance in determining protein topology. Physica A
    38. (2003). Emerging ideas on the molecular basis of protein and peptide aggregation.
    39. (2007). Exploring subdomain cooperativity in T4 lysozyme II: Uncovering the C-terminal subdomain as a hidden intermediate in the kinetic folding pathway. Protein Sci.
    40. (2003). Exploring the interplay between topology and secondary structural formation in the protein folding problem.
    41. (1999). Exploring the origins of topological frustration: Design of a minimally frustrated model of fragment B of protein A.
    42. (2008). Extracting function from a beta-trefoil folding motif.
    43. (2002). Flexibility and packing in proteins.
    44. (2007). Fly-casting in protein-DNA binding: Frustration between protein folding and electrostatics facilitates target recognition.
    45. (2002). Folding and stretching in a Go-like model of titin. Proteins
    46. (2008). Folding mechanisms of individual beta-hairpins in a Go model of Pin1 WW domain by all-atom molecular dynamics simulations.
    47. (2003). Folding of Cu, Zn superoxide dismutase and familial amyotrophic lateral sclerosis.
    48. (2002). Folding pathways of prion and
    49. (1997). Folding thermodynamics of a model three-helix-bundle protein.
    50. (2006). Folding with downhill behavior and low cooperativity of proteins. Proteins
    51. (2006). Folding-based molecular simulations reveal mechanisms of the rotary motor F-1-ATPase.
    52. (2009). Functional diversity and shifting cores of stability modulate the folding mechanisms of flavodoxin fold proteins.
    53. (1999). Go-ing for the prediction of protein folding mechanisms.
    54. (2007). How well can we understand large-scale protein motions using normal modes of elastic network models?
    55. (2007). Hydrophobic cooperativity as a mechanism for amyloid nucleation.
    56. (2009). Identifying the protein folding nucleus using molecular dynamics.
    57. (2003). Improved Go-like models demonstrate the robustness of protein folding mechanisms towards non-native interactions.
    58. (2007). Influence of the chain stiffness on the thermodynamics of a Go-type model for protein folding.
    59. (2007). Influence of the native topology on the folding barrier for small proteins.
    60. (2006). Insertion and assembly of membrane proteins via simulation.
    61. (2004). Integrating folding kinetics and protein function: Biphasic kinetics and dual binding specificity in a WW domain.
    62. (2003). Interplay among tertiary contacts, secondary structure formation and side-chain packing in the protein folding mechanism: All-atom representation study of protein
    63. (2005). Intrinsically unstructured proteins and their functions.
    64. (2006). Kinetic definition of protein folding transition state ensembles and reaction coordinates.
    65. (2008). Kinetic traps in the folding of beta alpha-repeat proteins: CheY initially misfolds before accessing the native conformation.
    66. (2005). Large amplitude conformational change in proteins explored with a plastic network model: Adenylate kinase.
    67. (2007). Localizing frustration in native proteins and protein assemblies.
    68. (2007). Mechanical stretching of proteins: A theoretical survey of the Protein Data Bank.
    69. (2008). Microseconds dynamics simulations of the outer-membrane protease
    70. (2002). Molecular dynamics simulation of the SH3 domain aggregation suggests a generic amyloidogenesis mechanism.
    71. (2006). Molecular dynamics simulations of outer-membrane protease T from E-coli based on a hybrid coarse-grained/atomistic potential.
    72. (2006). Multiple routes lead to the native state in the energy landscape of the beta-trefoil family.
    73. (2008). Multiscale methods for macromolecular simulations.
    74. (2002). Native and non-native interactions along protein folding and unfolding pathways. Proteins
    75. (2009). Native topology of the designed protein Top7 is not conducive to cooperative folding.
    76. (2007). Network analysis of protein dynamics. FEBS Lett.
    77. (2004). New insights into FAK signaling and localization based on detection of a FAT domain folding intermediate. Structure
    78. (2003). Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins.
    79. (2006). On the role of chemical detail in simulating protein folding kinetics.
    80. (1999). On the role of conformational geometry in protein folding.
    81. (1998). On the transition coordinate for protein folding.
    82. (1976). On the use of classical statistical mechanics in the treatment of polymer chain conformations. Macromolecules
    83. (2004). Optimal combination of theory and experiment for the characterization of the protein folding landscape of S6: How far can a minimalist model go?
    84. (2006). P versus Q: Structural reaction coordinates capture protein folding on smooth landscapes.
    85. (2007). Parallel foldng pathways in the SH3 domain protein.
    86. (2008). Peptide folding using multiscale coarse-grained models.
    87. (2004). Phi-Value analysis and the nature of protein-folding transition states.
    88. (2008). Predicting the order in which contacts are broken during single molecule protein stretching experiments. Proteins
    89. (1999). Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures.
    90. (2009). Protein cutoff scanning: A comparative analysis of cutoff dependent and cutoff free methods for prospecting contacts in proteins. Proteins
    91. (1991). Protein folding bottlenecks: A lattice Monte-Carlo simulation.
    92. (2007). Protein folding by zipping and assembly.
    93. (2002). Protein folding mediated by solvation: Water expulsion and formation of the hydrophobic core occur after the structural collapse.
    94. (2006). Protein folding thermodynamics and dynamics: Where physics, chemistry, and biology meet.
    95. (2005). Protein oligomerization through domain swapping: Role of inter-molecular interactions and protein concentration.
    96. (2007). Protein simulations combining an all-atom force field with a Go term.
    97. (2004). Protein topology determines binding mechanism.
    98. (2000). Proteins with similar architecture exhibit similar large-scale dynamic behavior.
    99. (2008). Protofibril assemblies of the arctic, dutch, and flemish mutants of the Alzheimer's A beta(1-40) peptide.
    100. (2006). Pulling single bacteriorhodopsin out of a membrane: Comparison of simulation and experiment.
    101. (2009). Quantitative criteria for native energetic heterogeneity influences in the prediction of protein folding kinetics.
    102. (2008). Rate constant and reaction coordinate of Trp-cage folding in explicit water.
    103. (2007). Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin.
    104. (2002). Residue packing in proteins: Uniform distribution on a coarse-grained scale.
    105. (1996). Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading.
    106. (1978). Respective roles of short-range and long-range interactions in protein folding.
    107. (2001). Role of native-state topology in the stabilization of intracellular antibodies.
    108. (2001). Roles of native topology and chain-length scaling in protein folding: A simulation study with a Go-like
    109. (2008). Selection of optimal variants of Go-like models of proteins through studies of stretching.
    110. (2007). Self-assembly of beta-sheet forming peptides into chiral fibrillar aggregates.
    111. (2006). Sequence of events in folding mechanism: Beyond the Go model. Protein Sci.
    112. (2005). Simple energy landscape model for the kinetics of functional transitions in proteins.
    113. (2008). Simple physics-based analytical formulas for the potentials of mean force for the interaction of amino acid side chains in water. IV. Pairs of different hydrophobic side chains.
    114. (2008). Simulations of the protein folding process using topology-based models depend on the experimental structure.
    115. (2005). Slow protein conformational dynamics from multiple experimental structures: The helix/sheet transition of arc repressor. Structure
    116. (2004). Small-world communication of residues and significance for protein dynamics.
    117. (2002). Small-world view of the amino acids that play a key role in protein folding.
    118. (2003). Solvation effects and driving forces for protein thermodynamic and kinetic cooperativity: How adequate is native-centric topological modeling?
    119. (2006). Spontaneous fibril formation by polyalanines; Discontinuous molecular dynamics simulations.
    120. (2008). Stabilizing effect of knots on proteins.
    121. (2001). Statistical thermodynamics: Taking a walk on a landscape. Science
    122. (2007). Structural analysis of kinetic folding intermediates for a TIM barrel protein, indole-3-glycerol phosphate synthase, by hydrogen exchange mass spectrometry and Go model simulation.
    123. (2007). Structural change and nucleotide dissociation of myosin motor domain: Dual Go model simulation.
    124. (1996). Structure of the transition state for folding of the 129 aa protein CheY resembles that of a smaller protein,
    125. (1996). Structure-based calculation of the equilibrium folding pathway of proteins. Correlation with hydrogen exchange protection factors.
    126. (2006). Structure-function-folding relationship in a WW domain.
    127. Studies on protein folding, unfolding and fluctuations by computer simulation. 1. Effect of specific amino acid sequence represented by specific inter-unit interactions.
    128. (1978). Studies on protein folding, unfolding and fluctuations by computer simulation. 2. A three-dimensional lattice model of lysozyme. Biopolymers
    129. (1979). Studies on protein folding, unfolding and fluctuations by computer simulation. 3. Effect of short-range interactions.
    130. (1979). Studies on protein folding, unfolding and fluctuations by computer simulation. 4. Hydrophobic interactions.
    131. (2008). Subdomain competition, cooperativity, and topological frustration in the folding of
    132. (2007). Temperature-dependent folding pathways of pin1 WW domain: An all-atom molecular dynamics simulation of a Go model.
    133. (2006). The crystal structure of beryllofluoride Spo0F in complex with the phosphotransferase Spo0B represents a phosphotransfer pretransition
    134. (1988). The effect of amino acid substitution on protein folding and protein unfolding transition studied by computer simulation.
    135. (2004). The effects of nonnative interactions on protein folding rates: Theory and simulation. Protein Sci.
    136. (2005). The energy landscape of modular repeat proteins: Topology determines folding mechanism in the ankyrin family.
    137. (2002). The ensemble folding kinetics of protein G from an all-atom Monte Carlo simulation.
    138. (2005). The equilibrium properties and folding kinetics of an allatom Go model of the Trp-cage.
    139. (2001). The folding thermodynamics and kinetics of crambin using an all-atom Monte Carlo simulation.
    140. (2003). The importance of explicit chain representation in protein folding models: An examination of Ising-like models. Proteins
    141. (2007). The length dependence of the PolyQ-mediated protein aggregation.
    142. The MARTINI coarse-grained force field: Extension to proteins.
    143. (2007). The mechanical unfolding of ubiquitin through all-atom Monte Carlo simulation with a Go-type potential.
    144. (2005). The native energy landscape for interleukin-1 beta. Modulation of the population ensemble through nativestate topology.
    145. (2002). The origins of asymmetry in the folding transition states of protein L and protein
    146. (2008). The protein folding problem.
    147. (2005). The role of shape in determining molecular motions.
    148. (2002). The role of sidechain packing and native contact interactions in folding: Discontinuous molecular dynamics folding simulations of an all-atom Go model of fragment
    149. (2008). Theoretical and experimental demonstration of the importance of specific nonnative interactions in protein folding.
    150. (1983). Theoretical studies of protein folding.
    151. (1976). Theory of large-amplitude conformational fluctuations in native globular proteins: Independent fluctuating site model.
    152. (2004). Theory of protein folding.
    153. (2002). Thermodynamics of an all-atom off-lattice model of the fragment B of Staphylococcal protein A: Implication for the origin of the cooperativity of protein folding.
    154. (2005). Thermodynamics of Go-type models for protein folding.
    155. (2000). 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.
    156. (2002). Topological determinants of protein folding.
    157. (2006). Topological frustration and the folding of interleukin-1 beta.
    158. Topology-based models and NMR structures in protein folding simulations.
    159. Toward a coarse-grained protein model coupled with a coarsegrained solvent model: Solvation free energies of amino acid side chains.
    160. (2000). Towards understanding a molecular switch mechanism: Thermodynamic and crystallographic studies of the signal transduction protein
    161. (2001). Two-state allosteric behavior in a singledomain signaling protein. Science
    162. (2003). Uncovering network systems within protein structures.
    163. (2003). Universality classes in folding times of proteins.
    164. (2002). Validity of Go models: Comparison with a solventshielded empirical energy decomposition.

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