We have made significant progress in several areas related to protein dynamics, folding, and function. (1) Protein dynamics. We have developed a coarse-grained model that allows us to explore conformational transitions of proteins in the microsecond to millisecond regime. In an initial application, we showed that the helix-to-sheet transition in the DNA binding interface of an Arc repressor mutant proceeds through an unfolded intermediate (Best, Chen, and Hummer, Structure, 2005). (2) Protein hydration. In collaboration with the experimental groups of Sol Gruner (Cornell) and Brian Matthews (HHMI), we provided the first direct demonstration of cooperative water penetration into a nonpolar cavity in the interior of a protein (Collins et al., Proc. Natl. Acad. Sci. USA, 2005). For this study, we combined high-pressure X-ray crystallography and molecular dynamics simulations. (3) Proton translocation. In collaboration with Sergio Hassan and Yong-Sok Lee (CIT), we studied proton translocation along an oriented water chain at quantum mechanical detail (J. Chem. Phys. 2006). We demonstrated that transfer from a donor to an overall neutral acceptor can be remarkably fast (~1 ps along ~5-water chain), but the rate is highly sensitive to perturbations by local electric fields. These results suggest possible gating mechanisms for biological proton transfer. In a separate study, we showed that the time it takes an ion to traverse a membrane channel is independent of the direction, thermodynamically uphill or downhill (Berezhkovskii, Hummer, Bezrukov, Phys. Rev. Lett., 2006). (4) Protein folding. By using a coarse-grained model, we demonstrated that the search of protein conformation space is well described by 1D Brownian dynamics, with an effective diffusion coefficient that is determined by local barrier crossing events such as dihedral angle transitions (Best and Hummer, Phys. Rev. Lett. 2006). (5) Single-molecule biophysics. We have developed a unified theory of force induced molecular transitions (Dudko, Hummer, Szabo, Phys. Rev. Lett., 2006). Initial applications to DNA unzipping experiments produce very promising results.
| Rosta, Edina; Buchete, Nicolae-Viorel; Hummer, Gerhard (2009) Thermostat artifacts in replica exchange molecular dynamics simulations. J Chem Theory Comput 5:1393-1399 |
| Best, Robert B; Hummer, Gerhard (2009) Biochemistry. Unfolding the secrets of calmodulin. Science 323:593-4 |
| Tikhonova, Irina G; Best, Robert B; Engel, Stanislav et al. (2008) Atomistic insights into rhodopsin activation from a dynamic model. J Am Chem Soc 130:10141-9 |
| Turjanski, Adrian Gustavo; Gutkind, J Silvio; Best, Robert B et al. (2008) Binding-induced folding of a natively unstructured transcription factor. PLoS Comput Biol 4:e1000060 |
| Kim, Young C; Tang, Chun; Clore, G Marius et al. (2008) Replica exchange simulations of transient encounter complexes in protein-protein association. Proc Natl Acad Sci U S A 105:12855-60 |
| Best, Robert B; Buchete, Nicolae-Viorel; Hummer, Gerhard (2008) Are current molecular dynamics force fields too helical? Biophys J 95:L07-9 |
| Buchete, Nicolae-Viorel; Hummer, Gerhard (2008) Peptide folding kinetics from replica exchange molecular dynamics. Phys Rev E Stat Nonlin Soft Matter Phys 77:030902 |
| Buchete, Nicolae-Viorel; Hummer, Gerhard (2008) Coarse master equations for peptide folding dynamics. J Phys Chem B 112:6057-69 |
| Kim, Young C; Hummer, Gerhard (2008) Coarse-grained models for simulations of multiprotein complexes: application to ubiquitin binding. J Mol Biol 375:1416-33 |
| Canagarajah, Bertram J; Hummer, Gerhard; Prinz, William A et al. (2008) Dynamics of cholesterol exchange in the oxysterol binding protein family. J Mol Biol 378:737-48 |
Showing the most recent 10 out of 42 publications
