Research Topics
| Robert B BestSummaryAffiliation: University of Cambridge Country: UK Publications
| Collaborators
|
Detail Information
Publications
Structural interpretation of hydrogen exchange protection factors in proteins: characterization of the native state fluctuations of CI2Robert 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...
Residue-specific α-helix propensities from molecular simulationRobert 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...- Inclusion of many-body effects in the additive CHARMM protein CMAP potential results in enhanced cooperativity of α-helix and β-hairpin formationRobert 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... 
Atomistic molecular simulations of protein foldingRobert 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...- Protein simulations with an optimized water model: cooperative helix formation and temperature-induced unfolded state collapseRobert 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... - Optimized molecular dynamics force fields applied to the helix-coil transition of polypeptidesRobert 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... - Coordinate-dependent diffusion in protein foldingRobert 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... - Balance between alpha and beta structures in ab initio protein foldingRobert 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... - Effect of flexibility and cis residues in single-molecule FRET studies of polyprolineRobert 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... - Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differencesRobert B Best
Department of Chemistry, University of Cambridge, Cambridge UK
Proteins 79:1318-28. 2011.... - Diffusion models of protein foldingRobert 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... - Hydrophobic core fluidity of homologous protein domains: relation of side-chain dynamics to core composition and packingRobert B Best
Cambridge University Chemical Laboratory, MRC Centre for Protein Engineering, Lensfield Road, Cambridge CB2 1EW, UK
Biochemistry 43:1145-55. 2004.... - Crosstalk between the protein surface and hydrophobic core in a core-swapped fibronectin type III domainKate 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... - Mechanical unfolding of a titin Ig domain: structure of transition state revealed by combining atomic force microscopy, protein engineering and molecular dynamics simulationsRobert 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... - Characterizing the unfolded states of proteins using single-molecule FRET spectroscopy and molecular simulationsKusai 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.... - Mechanical unfolding of a titin Ig domain: structure of unfolding intermediate revealed by combining AFM, molecular dynamics simulations, NMR and protein engineeringSusan 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... - Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteinsMadeleine 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... - Structural comparison of the two alternative transition states for folding of TI I27Christian 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.... - Characterization of the residual structure in the unfolded state of the Delta131Delta fragment of staphylococcal nucleaseChristopher 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... - The origin of protein sidechain order parameter distributionsRobert 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... - Diffusive model of protein folding dynamics with Kramers turnover in rateRobert B Best
Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0520, USA
Phys Rev Lett 96:228104. 2006.... - Designing an extracellular matrix protein with enhanced mechanical stabilitySean 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... - Reaction coordinates and rates from transition pathsRobert 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... - Thermodynamics and kinetics of protein folding under confinementJeetain 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... - Relation between native ensembles and experimental structures of proteinsRobert 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.... - Pulling direction as a reaction coordinate for the mechanical unfolding of single moleculesRobert 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... - What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation analysisRobert 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... - Evidence for a partially structured state of the amylin monomerSara 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... - 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... - Binding-induced folding of a natively unstructured transcription factorAdrian 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... - 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 - Protein folding kinetics under force from molecular simulationRobert 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... - Simultaneous determination of protein structure and dynamicsKresten 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... - Modulation of an IDP binding mechanism and rates by helix propensity and non-native interactions: association of HIF1α with CBPDavid 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... - Atomistic insights into rhodopsin activation from a dynamic modelIrina 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.... - Determination of protein structures consistent with NMR order parametersRobert 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... - A preformed binding interface in the unbound ensemble of an intrinsically disordered protein: evidence from molecular simulationsMichael 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... - Microscopic events in β-hairpin folding from alternative unfolded ensemblesRobert 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... - A simple method for probing the mechanical unfolding pathway of proteins in detailRobert 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... - Slow protein conformational dynamics from multiple experimental structures: the helix/sheet transition of arc repressorRobert 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... - 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... - 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... - Hidden complexity in the mechanical properties of titinPhilip 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... - A mutant chaperonin with rearranged inter-ring electrostatic contacts and temperature-sensitive dissociationB 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... - Interpreting dynamically-averaged scalar couplings in proteinsKresten 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....