I have recently moved to the National Institutes of Health; please see my new website here:
My research is concerned with the dynamics of large biomolecules, in particular with protein dynamics, folding and binding. Through the impressive achievements of structural biology, much has been learnt about the function of proteins by solving the structures of their stable states (e.g. active, inactive conformations). Studying the dynamics and mechanism of transitions between these states is still a major challenge for both experiment and simulation, yet is equally important for understanding function. I develop novel methods for studying macromolecular dynamics and apply them to biologically interesting systems, using a combination of simulation and theory appropriate for addressing each question.
For example, we have devised algorithms for enhanced sampling of the “rare events” in simulations, which constitute the reactive portions of the trajectory; by designing good “reaction coordinates”, we are able to describe the progress of the reaction (mechanism) quantitatively. To study larger systems or longer time scales, we are developing coarse-grained models with reduced complexity. We have also devised improvements to all-atom simulation models, towards the goal of more accurately simulating protein folding and the mechanism of coupled folding and binding. We work closely with experimental collaborators, either by using theory to help in interpreting experiments or experimental data to refine simulation methodology. We have used coarse-grained models to help interpret single molecule protein folding experiments based on fluorescence resonance energy transfer or atomic force microscopy and all-atom models to interpret NMR dynamics experiments.
Using ligand-mapping simulations to design a ligand selectively targeting a cryptic surface pocket of polo-like kinase 1
YS Tan, P Śledź, S Lang, CJ Stubbs, DR Spring, C Abell, RB Best – Angew Chem Int Ed Engl (2012
Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone phi, psi and Side-Chain chi(1) and chi(2) Dihedral Angles
RB Best, X Zhu, J Shim, PEM Lopes, J Mittal, M Feig, AD MacKerell Jr – Journal of Chemical Theory and Computation (2012
Inclusion of many-body effects in the additive CHARMM protein CMAP potential results in enhanced cooperativity of α-helix and β-hairpin formation.
RB Best, J Mittal, M Feig, AD MacKerell Jr – Biophysical Journal (2012
Smoothing of the GB1 hairpin folding landscape by interfacial confinement
A Bhattacharya, RB Best, J Mittal – Biophysical Journal (2012
A Preformed Binding Interface in the Unbound Ensemble of an Intrinsically Disordered Protein: Evidence from Molecular Simulations
M Knott, RB Best – PLoS Comput Biol (2012
Force-Field Dependence of Chignolin Folding and Misfolding: Comparison with Experiment and Redesign
P Kührová, A De Simone, M Otyepka, RB Best – Biophysical Journal (2012
Peptide Chain Dynamics in Light and Heavy Water: Zooming in on Internal Friction
JCF Schulz, L Schmidt, RB Best, J Dzubiella, RR Netz – Journal of the American Chemical Society (2012
Residue-specific α-helix propensities from molecular simulation.
RB Best, D de Sancho, J Mittal – Biophysical Journal (2012
Atomistic molecular simulations of protein folding
RB Best – Current Opinion in Structural Biology (2012
Modulation of an IDP binding mechanism and rates by helix propensity and non-native interactions: association of HIF1 alpha with CBP
D De Sancho, RB Best – Molecular BioSystems (2012
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