Robert B Best

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. ncbi request reprint Structural interpretation of hydrogen exchange protection factors in proteins: characterization of the native state fluctuations of CI2
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
    Structure 14:97-106. 2006
  2. pmc A preformed binding interface in the unbound ensemble of an intrinsically disordered protein: evidence from molecular simulations
    Michael Knott
    University of Cambridge, Department of Chemistry, Cambridge, United Kingdom
    PLoS Comput Biol 8:e1002605. 2012
  3. pmc Residue-specific α-helix propensities from molecular simulation
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Biophys J 102:1462-7. 2012
  4. pmc Inclusion of many-body effects in the additive CHARMM protein CMAP potential results in enhanced cooperativity of α-helix and β-hairpin formation
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Biophys J 103:1045-51. 2012
  5. doi request reprint Atomistic molecular simulations of protein folding
    Robert B Best
    University of Cambridge, Department of Chemistry, Cambridge CB2 1EW, United Kingdom
    Curr Opin Struct Biol 22:52-61. 2012
  6. doi request reprint Balance between alpha and beta structures in ab initio protein folding
    Robert B Best
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK
    J Phys Chem B 114:8790-8. 2010
  7. pmc Effect of flexibility and cis residues in single-molecule FRET studies of polyproline
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520, USA
    Proc Natl Acad Sci U S A 104:18964-9. 2007
  8. doi request reprint Protein simulations with an optimized water model: cooperative helix formation and temperature-induced unfolded state collapse
    Robert B Best
    Cambridge University, Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    J Phys Chem B 114:14916-23. 2010
  9. ncbi request reprint Hydrophobic core fluidity of homologous protein domains: relation of side-chain dynamics to core composition and packing
    Robert B Best
    Cambridge University Chemical Laboratory, MRC Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, UK
    Biochemistry 43:1145-55. 2004
  10. doi request reprint Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differences
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge UK
    Proteins 79:1318-28. 2011

Collaborators

Detail Information

Publications54

  1. ncbi request reprint Structural interpretation of hydrogen exchange protection factors in proteins: characterization of the native state fluctuations of CI2
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
    Structure 14:97-106. 2006
    ..The method is applied to determine the ensemble of structures representing the native state of chymotrypsin inhibitor 2 (CI2), including the rare, large fluctuations responsible for hydrogen exchange...
  2. pmc A preformed binding interface in the unbound ensemble of an intrinsically disordered protein: evidence from molecular simulations
    Michael Knott
    University of Cambridge, Department of Chemistry, Cambridge, United Kingdom
    PLoS Comput Biol 8:e1002605. 2012
    ..We obtain support for this mechanism from coarse-grained simulations of NCBD with, and without, its binding partner...
  3. pmc Residue-specific α-helix propensities from molecular simulation
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Biophys J 102:1462-7. 2012
    ..The resulting parameters should more faithfully reproduce helix propensities in simulations of protein folding and disordered proteins...
  4. pmc Inclusion of many-body effects in the additive CHARMM protein CMAP potential results in enhanced cooperativity of α-helix and β-hairpin formation
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Biophys J 103:1045-51. 2012
    ..These results suggest that the revised energy function will be suitable for both simulations of unfolded or intrinsically disordered proteins and for investigating protein-folding mechanisms...
  5. doi request reprint Atomistic molecular simulations of protein folding
    Robert B Best
    University of Cambridge, Department of Chemistry, Cambridge CB2 1EW, United Kingdom
    Curr Opin Struct Biol 22:52-61. 2012
    ..I also attempt to place atomistic models into the context of the energy landscape view of protein folding, and coarse-grained simulations...
  6. doi request reprint Balance between alpha and beta structures in ab initio protein folding
    Robert B Best
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK
    J Phys Chem B 114:8790-8. 2010
    ..Our results suggest that the backbone correction results in a force field that is transferable to the folding of proteins from different structural classes...
  7. pmc Effect of flexibility and cis residues in single-molecule FRET studies of polyproline
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520, USA
    Proc Natl Acad Sci U S A 104:18964-9. 2007
    ..A similar simulation approach suggests that the flexibility of the chromophore linkers is largely responsible for the previously unexplained high value of R(0) required to fit the data in the classic study of Stryer and Haugland...
  8. doi request reprint Protein simulations with an optimized water model: cooperative helix formation and temperature-induced unfolded state collapse
    Robert B Best
    Cambridge University, Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    J Phys Chem B 114:14916-23. 2010
    ..These results together suggest that Amber ff03w (with TIP4P/2005) will be well suited for studying protein folding and properties of unfolded state and intrinsically disordered proteins over a wide range of thermodynamic conditions...
  9. ncbi request reprint Hydrophobic core fluidity of homologous protein domains: relation of side-chain dynamics to core composition and packing
    Robert B Best
    Cambridge University Chemical Laboratory, MRC Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, UK
    Biochemistry 43:1145-55. 2004
    ....
  10. doi request reprint Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differences
    Robert B Best
    Department of Chemistry, University of Cambridge, Cambridge UK
    Proteins 79:1318-28. 2011
    ....
  11. pmc Diffusion models of protein folding
    Robert B Best
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Phys Chem Chem Phys 13:16902-11. 2011
    ..Lastly, we consider how our results are useful for the interpretation of experiments, and how this type of Bayesian analysis may eventually be applied directly to analyse experimental data...
  12. pmc Optimized molecular dynamics force fields applied to the helix-coil transition of polypeptides
    Robert B Best
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U K
    J Phys Chem B 113:9004-15. 2009
    ..Our structural and thermodynamic analyses point toward the physical origins of these shortcomings in current force fields, and suggest ways to address them in future force-field development...
  13. pmc Coordinate-dependent diffusion in protein folding
    Robert B Best
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    Proc Natl Acad Sci U S A 107:1088-93. 2010
    ..Lastly, we comment on the design of future single-molecule experiments that probe the position dependence of D directly...
  14. pmc Crosstalk between the protein surface and hydrophobic core in a core-swapped fibronectin type III domain
    Kate S Billings
    Cambridge University Chemical Laboratory, MRC Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, UK
    J Mol Biol 375:560-71. 2008
    ..For example, the anomalous response of FNfn10 to mutation is not solely a property of the core as we had previously suggested...
  15. ncbi request reprint Mechanical unfolding of a titin Ig domain: structure of transition state revealed by combining atomic force microscopy, protein engineering and molecular dynamics simulations
    Robert B Best
    Department of Chemistry, University of Cambridge, MRC Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, UK
    J Mol Biol 330:867-77. 2003
    ..This explains the correspondence between hierarchy of kinetic stability (measured in stopped-flow denaturant studies) and mechanical strength in these titin domains...
  16. pmc Characterizing the unfolded states of proteins using single-molecule FRET spectroscopy and molecular simulations
    Kusai A Merchant
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520, USA
    Proc Natl Acad Sci U S A 104:1528-33. 2007
    ....
  17. ncbi request reprint Mechanical unfolding of a titin Ig domain: structure of unfolding intermediate revealed by combining AFM, molecular dynamics simulations, NMR and protein engineering
    Susan B Fowler
    University of Cambridge, Department of Chemistry, MRC Centre for Protein Engineering, UK
    J Mol Biol 322:841-9. 2002
    ..Comparison with a Phi-value analysis of the unfolding pathway clearly shows that the protein unfolds by a different pathway under an applied force than on addition of denaturant...
  18. pmc Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins
    Madeleine B Borgia
    University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK
    Nature 474:662-5. 2011
    ..Diversifying the sequence between neighbouring domains seems to be a successful evolutionary strategy to avoid misfolding in multidomain proteins...
  19. pmc Structural comparison of the two alternative transition states for folding of TI I27
    Christian D Geierhaas
    Department of Chemistry, Medical Research Council Centre for Protein Engineering, University of Cambridge, Cambridge CB2 1EW, United Kingdom
    Biophys J 91:263-75. 2006
    ....
  20. ncbi request reprint Characterization of the residual structure in the unfolded state of the Delta131Delta fragment of staphylococcal nuclease
    Christopher J Francis
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Proteins 65:145-52. 2006
    ..Only rarely, however, all these interactions are simultaneously realized to generate conformations with an overall native topology...
  21. ncbi request reprint The origin of protein sidechain order parameter distributions
    Robert B Best
    MRC Centre for Protein Engineering, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK
    J Am Chem Soc 126:7734-5. 2004
    ..This result will aid in the interpretation of data from NMR dynamics experiments...
  22. pmc Binding-induced folding of a natively unstructured transcription factor
    Adrian Gustavo Turjanski
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Comput Biol 4:e1000060. 2008
    ..The simulations are in general agreement with the results of a recently reported nuclear magnetic resonance study, and aid in the interpretation of the experimental binding kinetics...
  23. ncbi request reprint Diffusive model of protein folding dynamics with Kramers turnover in rate
    Robert B Best
    Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0520, USA
    Phys Rev Lett 96:228104. 2006
    ....
  24. pmc Reaction coordinates and rates from transition paths
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 132, Bethesda, MD 20892 0520, USA
    Proc Natl Acad Sci U S A 102:6732-7. 2005
    ..The resulting one-dimensional reaction coordinate captures the folding transition state, with formation and packing of helix 2 and 3 constituting the bottleneck for folding...
  25. pmc Thermodynamics and kinetics of protein folding under confinement
    Jeetain Mittal
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520, USA
    Proc Natl Acad Sci U S A 105:20233-8. 2008
    ..The diffusion coefficients only change in the unfolded state basin, where they are increased because of compaction...
  26. pmc Designing an extracellular matrix protein with enhanced mechanical stability
    Sean P Ng
    Cambridge University Chemical Laboratory, Medical Research Council Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    Proc Natl Acad Sci U S A 104:9633-7. 2007
    ..Thus, we have specifically designed a protein with increased mechanical stability. Our results demonstrate that core engineering can be used to change the mechanical strength of proteins while retaining functional surface interactions...
  27. pmc Relation between native ensembles and experimental structures of proteins
    Robert B Best
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    Proc Natl Acad Sci U S A 103:10901-6. 2006
    ....
  28. pmc Are current molecular dynamics force fields too helical?
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0520, USA
    Biophys J 95:L07-9. 2008
    ..We conclude that radical changes to the best current force fields are not necessary, based on the NMR data. Nevertheless, experiments on short peptides open the way toward the systematic improvement of current simulation models...
  29. ncbi request reprint What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation analysis
    Robert B Best
    MRC Centre for Protein Engineering, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK
    J Mol Biol 349:185-203. 2005
    ..A statistical analysis of published order parameters supports the conclusions drawn from the simulations...
  30. doi request reprint Pulling direction as a reaction coordinate for the mechanical unfolding of single molecules
    Robert B Best
    Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Phys Chem B 112:5968-76. 2008
    ..The apparent similarity between extrapolated and intrinsic rates in experiments, unexpected for different unfolding barriers, can be explained if the turnover occurs at low forces...
  31. pmc Evidence for a partially structured state of the amylin monomer
    Sara M Vaiana
    Laboratory of Chemical Physics, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Biophys J 97:2948-57. 2009
    ..We discuss these newly observed differences between human and rat amylin in solution and their possible relation to aggregation and to the physiological function of amylin binding to the calcitonin receptor...
  32. ncbi request reprint Comment on "Force-clamp spectroscopy monitors the folding trajectory of a single protein"
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes andDigestive and Kidney Diseases, National Institutes of Health, Building 5, Bethesda MD 20892 0520, USA
    Science 308:498; author reply 498. 2005
  33. doi request reprint Protein folding kinetics under force from molecular simulation
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0520, USA
    J Am Chem Soc 130:3706-7. 2008
    ..Our findings explain why refolding becomes very slow at even moderate pulling forces and suggest how it could be practically observed in experiments at higher forces...
  34. pmc Engineering folding dynamics from two-state to downhill: application to λ-repressor
    JAMES W CARTER
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    J Phys Chem B 117:13435-43. 2013
    ....
  35. pmc How well does a funneled energy landscape capture the folding mechanism of spectrin domains?
    Robert B Best
    Department of Chemistry, Cambridge University, Lensfield Road Cambridge CB2 1EW, U K
    J Phys Chem B 117:13235-44. 2013
    ....
  36. ncbi request reprint Simultaneous determination of protein structure and dynamics
    Kresten Lindorff-Larsen
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Nature 433:128-32. 2005
    ..The protocol is completely general and should lead to significant advances in our ability to understand and utilize the structures of native proteins...
  37. doi request reprint Modulation of an IDP binding mechanism and rates by helix propensity and non-native interactions: association of HIF1α with CBP
    David De Sancho
    Cambridge University, Department of Chemistry, Cambridge, UK
    Mol Biosyst 8:256-67. 2012
    ..Transition state structures for the three models are highly disordered, supporting a fly-casting mechanism for binding...
  38. pmc Atomistic insights into rhodopsin activation from a dynamic model
    Irina G Tikhonova
    Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Am Chem Soc 130:10141-9. 2008
    ....
  39. ncbi request reprint Determination of protein structures consistent with NMR order parameters
    Robert B Best
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    J Am Chem Soc 126:8090-1. 2004
    ..The latter effectively acts as a sophisticated motional model, allowing ensembles of structures consistent with the experimental order parameters to be determined...
  40. ncbi request reprint Complex energy landscape of a giant repeat protein
    Maksym Tsytlonok
    MRC Cancer Cell Unit, Hutchison MRC Research Centre, Hills Road, Cambridge CB2 0XZ, UK Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Structure 21:1954-65. 2013
    ..Partial unfolding of PR65/A also impacts catalysis by altering the proximity of bound catalytic subunit and substrate. Thus, the repeat array orchestrates the assembly and activity of PP2A. ..
  41. pmc Native contacts determine protein folding mechanisms in atomistic simulations
    Robert B Best
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520
    Proc Natl Acad Sci U S A 110:17874-9. 2013
    ..More remarkably, however, we found that for almost all the proteins, with the designed protein α3D being a notable exception, nonnative contacts play no significant part in determining folding mechanisms. ..
  42. pmc Microscopic events in β-hairpin folding from alternative unfolded ensembles
    Robert B Best
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    Proc Natl Acad Sci U S A 108:11087-92. 2011
    ..The lengths of transition paths span a wide range, from 50 ps to 140 ns, at 300 K...
  43. pmc A simple method for probing the mechanical unfolding pathway of proteins in detail
    Robert B Best
    Department of Chemistry, Medical Research Council Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    Proc Natl Acad Sci U S A 99:12143-8. 2002
    ..The applicability of the method is tested on simulated data sets and experimental data for mutants of titin I27...
  44. pmc Comparing a simple theoretical model for protein folding with all-atom molecular dynamics simulations
    Eric R Henry
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520
    Proc Natl Acad Sci U S A 110:17880-5. 2013
    ....
  45. pmc Effects of interactions with the GroEL cavity on protein folding rates
    Anshul Sirur
    University of Cambridge, Department of Chemistry, Cambridge, United Kingdom
    Biophys J 104:1098-106. 2013
    ..The origin of the slowdown appears to be stabilization--relative to repulsive confinement--of the unfolded state through binding to the cavity walls, rather than a reduction of the diffusion coefficient along the folding coordinate...
  46. ncbi request reprint Slow protein conformational dynamics from multiple experimental structures: the helix/sheet transition of arc repressor
    Robert B Best
    Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Structure 13:1755-63. 2005
    ..Transient local unfolding is consistent with the low hydrogen exchange protection factors of the switch region. Also in agreement with experiment, the isomerization occurs independently of the global folding/dimerization transition...
  47. ncbi request reprint Molecular origins of internal friction effects on protein-folding rates
    David De Sancho
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Nat Commun 5:4307. 2014
    ..This insensitivity of local barrier crossing to solvent friction is expected to contribute to the viscosity dependence of folding rates in larger proteins. ..
  48. doi request reprint Effect of interactions with the chaperonin cavity on protein folding and misfolding
    Anshul Sirur
    Cambridge University, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK
    Phys Chem Chem Phys 16:6358-66. 2014
    ....
  49. doi request reprint What is the time scale for α-helix nucleation?
    David De Sancho
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK
    J Am Chem Soc 133:6809-16. 2011
    ..Despite the fast observed relaxation, the helix nucleation time is estimated from our model to be 20-70 ns at 300 K, with a dependence on temperature well described by Arrhenius kinetics...
  50. ncbi request reprint Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model
    Michael Knott
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    J Chem Phys 140:175102. 2014
    ..Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD. ..
  51. doi request reprint Force-induced change in protein unfolding mechanism: discrete or continuous switch?
    Thomas G W Graham
    Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK
    J Phys Chem B 115:1546-61. 2011
    ..We discuss the implications of the switch in pathway for the mechanical strength of proteins, and how such a switch may be experimentally tested...
  52. ncbi request reprint Hidden complexity in the mechanical properties of titin
    Philip M Williams
    Laboratory of Biophysics and Surface Analysis, School of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK
    Nature 422:446-9. 2003
    ..We also propose a unified forced unfolding model of all I27 analogues studied, and conclude that I27 can withstand higher forces in muscle than was predicted previously...
  53. ncbi request reprint Interpreting dynamically-averaged scalar couplings in proteins
    Kresten Lindorff-Larsen
    Department of Biochemistry, Institute of Molecular Biology and Physiology, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen Ø, DK, Denmark
    J Biomol NMR 32:273-80. 2005
    ....
  54. ncbi request reprint A mutant chaperonin with rearranged inter-ring electrostatic contacts and temperature-sensitive dissociation
    B Trevor Sewell
    Electron Microscope Unit and Department of Chemistry, University of Cape Town, Rondebosch, South Africa
    Nat Struct Mol Biol 11:1128-33. 2004
    ..Lacking the allosteric signal from the opposite ring, these complexes cannot release their GroES and become trapped, dead-end states...