个人简介

B.A., 1965, Harpur College M.S., 1967 and Ph.D., 1969, Princeton Univ. NATO Fellow, 1969, Lorentz Institute for Theoretical Physics Research Associate, 1971, Univ. of California-San Diego Alfred P. Sloan Research Fellow, 1976-80 Guggenheim Memorial Fellow, 1979-80 Co-Director: Quantitative Biology and Modeling Initiative AwardOrganizationDivisionLevel CodeType CodeStart DateEnd Date FellowJohn Simon Guggenheim FoundationProfessionalFellowship19791980 Alfred P. Sloan FellowshipAlfred P. Sloan FoundationProfessionalFellowship19761980 Ph.D.Princeton UniversityGraduateDegree1969 Postdoctoral FellowNATOPostdoctoralFellowship19691971 NBS Summer FellowNational Bureau of StandardsPostdoctoralFellowship1967 NIH Predoctoral FellowNational Institutes of HealthGraduateFellowship19671969 M.S.Princeton UniversityGraduateDegree1967 Bachelor of ArtsHarpur CollegeUndergraduateDegree1965 NSF TraineeNational Science FoundationGraduateHonors19651966

研究领域

Biological Physical Theoretical and Computational

(Research Description PDF - 791 kb) Statistical Mechanics and Quantum Mechanics are the methods we use to create theories and computational algorithms for the simulation of protein structure-function relations.A major effort is devoted to accelerating MD to reach realistic time scales. Another area of interest is ab initio molecular dynamics of electron localization in a variety of liquids. Ongoing studies include simulations and analysis of large-scale protein domain movements, proton translocation, and excess electron localization. Plot of committor versus end-to-end (EtoE) distance for the DIHED angle pathways. The first four strongest (highest overall flux) pathways are indicated: P1 solid line, P2 double line, P3 dashed line, and P4 dotted line. The sizes of the circles indicate the state populations. Also displayed are ensembles of backbone structures for the various states indicating the broad yet distinct conformations sampled . New methods are under development that can enhance the sampling of protein configurations to be able to explore the free energy cost for large domain motions. In the five residue opiod peptide met-enkephalin we have used long simulations along with a clustering and transition path analysis to obtain the major pathways of dihedral states visited for transitions between open and closed configurations and their correlation with committors (small values mean intermediate states return to initial state before visiting final state and vice versa). Leucine zippers (LZ) mediate the dimerization of proteins that regulate cellular activity, such as eukaryotic transcription factors. Generically, coiled coils form an important class of structural motifs. Francis Crick proposed the “knobs-into-holes” mode of packing, but electrostatic effects also play an important role in their stability. The LZ is a dimer and the determinants of its stability relative to monomers are our goal. We developed methods to simulate melting curves (fraction dimerized versus temperature) to study the stability of LZs as a function of their composition. A melting curve that contrasts a wild type (WT) LZ with an in silico mutant (MUT) that has neutralized most of the electrostatic interactions is displayed in the figure below. Wild type and mutant melting curves based on the native fraction, defined as the average number interactions that are broken in the LZ dimer. The three (two) traces for each WT (MUT) dimer stability definition are for the 3rd, 4th and 5th (3rd and 4th) ns of the HTREM simulation and show that the results have converged. The WT is more stable than the MUT indicating the importance of salt-bridges to LZ stability.

近期论文

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Nedialkov, Y. A., Opron, K., Assaf, F., Artsimovitch, I., Kireeva, M. L., Kashlev, M., Cukier, R. I., Nudler, E., and Burton, Z. F. (2013) The RNA polymerase bridge helix YFI motif in catalysis, fidelity and translocation. Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms 1829, 187-198 Liu, J. X., Wang, Z. P., Zhang, M., Cukier, R. I., and Bu, Y. X. (2013) Excess Dielectron in an Ionic Liquid as a Dynamic Bipolaron. Physical Review Letters 110 Wang, Z. P., Liu, J. X., Zhang, M., Cukier, R. I., and Bu, Y. X. (2012) Solvation and Evolution Dynamics of an Excess Electron in Supercritical CO2. Physical Review Letters Kireeva, M. L., Opron, K., Seibold, S. A., Domecq, C., Cukier, R. I., Coulombe, B., Kashlev, M., and Burton, Z. F. (2012) Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase. Bmc Biophys 5 Cukier, R. L. (2012) Simulations of Temperature and Salt Concentration Effects on bZIP, a Basic Region Leucine Zipper.Journal of Physical Chemistry B 116, 6071-6086 Cukier, R. I. (2011) Ferreting out correlations from trajectory data. J Chem Phys 135 Cukier, R. I. (2011) A Hamiltonian Replica Exchange Method for Building Protein-Protein Interfaces Applied to a Leucine Zipper.J. Chem. Phys. 134, 045104 Zhang, L. B., Chen, X. H., Liu, H. Y., Han, L., Cukier, R. I., and Bu, Y. X. (2010) Exploration of the Biological Micro-Surrounding Effect on the Excited States of the Size-Expanded Fluorescent Base x-Cytosine in DNA. Journal of Physical Chemistry B 114, 3726-3734 Wang, Z. P., Zhang, L., Cukier, R. I., and Bu, Y. X. (2010) States and migration of an excess electron in a pyridinium-based, room-temperature ionic liquid: an ab initio molecular dynamics simulation exploration. Physical Chemistry Chemical Physics 12, 1854-1861 Seibold, S. A., Singh, B. N., Zhang, C. F., Kireeva, M., Domecq, C., Bouchard, A., Nazione, A. M., Feig, M., Cukier, R. I., Coulombe, B., Kashlev, M., Hampsey, M., and Burton, Z. F. Conformational coupling, bridge helix dynamics and active site dehydration in catalysis by RNA polymerase. Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms 1799, 575-587 Cukier, R. I. (2010) How many atoms are required to characterize accurately trajectory fluctuations of a protein? The Journal of Chemical Physics 132, 245101 Chen, X. H., Zhang, L. B., Zhang, L., Sun, W. M., Zhang, Z. W., Liu, H. Y., Bu, Y. X., and Cukier, R. I. (2010) alpha-Helix C-Terminus Acting as a Relay to Mediate Long-Range Hole Migration in Proteins. Journal of Physical Chemistry Letters 1, 1637-1641 Zhang, L. B., Li, H. F., Chen, X. H., Cukier, R. I., and Bu, Y. X. (2009) Absorption and Fluorescence Emission Spectroscopic Characters of Size-Expanded yDNA Bases and Effect of Deoxyribose and Base Pairing. Journal of Physical Chemistry B 113, 1173-1181 Wang, Z. P., Zhang, L., Chen, X. H., Cukier, R. I., and Bu, Y. X. (2009) Excess Electron Solvation in an Imidazolium-Based Room-Temperature Ionic Liquid Revealed by Ab Initio Molecular Dynamics Simulations.Journal of Physical Chemistry B 113, 8222-8226 Wang, Z., Zhang, L., Chen, X., Cukier, R. I., and Bu, Y. (2009) Excess Electron Solvation in an Imidazolium-Based Room-Temperature Ionic Liquid Revealed by Ab Initio Molecular Dynamics Simulations. The Journal of Physical Chemistry B 113, 8222-8226 Su, L., and Cukier, R. I. (2009) Hamiltonian Replica Exchange Method Studies of a Leucine Zipper Dimer. The Journal of Physical Chemistry B 113, 9595-9605 Su, L., and Cukier, R. I. (2009) Hamiltonian Replica Exchange Method Study of E. coli and Y. pestis HPPK. The Journal of Physical Chemistry B 113, 16197–16208 Su, L., and Cukier, R. I. (2009) An Enhanced Molecular Dynamics Study of HPPK−ATP Conformation Space Exploration and ATP Binding to HPPK. The Journal of Physical Chemistry A 113, 2025-2035 Li, H. F., Zhang, L. B., Han, L., Cukier, R. I., and Bu, Y. X. (2009) Theoretical prediction of size-expansion effect on the C8-site activity in the modified guanine-cytosine analogs. Journal of Physical Organic Chemistry 22, 1114-1119 Han, L., Li, H. F., Cukier, R. I., and Bu, Y. X. (2009) Hetero-Ring-Expansion Design for Adenine-Based DNA Motifs: Evidence from DFT Calculations and Molecular Dynamics Simulations. Journal of Physical Chemistry B 113, 4407-4412