Statistical Mechanics and Quantum Mechanics are themethods we use to create theories
and computa- tional 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.
Plotof committor versus end-to-end (EtoE) distance for the DIHED angle pathways. The first
four strongest (highest overall flux) path- ways 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
opioid 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).
Protein stability is based on a delicate balance between energetic and entropic factors.
Intrinsically disordered proteins (IDPs) interacting with a folded partner protein
in the act of binding can order the IDP to form the correct functional interface by
decrease in the overall free energy. We develop methods evaluate the part of the entropic
cost of ordering an IDP arising from their dihedral states. As shown in the plot below,
the conformations based on the dihedral sampling is very dependent among all the dihedrals.
This leads to a reduction of the entropic cost of binding relative to independent
dihedral conformations.
Population fractions of the first 100 states sorted by decreasing size along with
the assumed inde- pendent state populations for those states. There are 312 = 531,441 possible states for the 6 phi and 6 psi three-conformation dihedrals. The
strong dependence among the dihedral conformers sam- pled is evident in this data
representation.
DihedralAngleEntropyMeasuresforIntrinsicallyDisorderedProteins, Cukier R. I., J. Phys. Chem. B 2015, 119, 3621−3634.
Conformational Transition of Response Regulator RR468 in a Two-Component System Signal
Transduction Process, Banerjee R. Yan H, and Cukier R. I., J.Phys.Chem. B 2014, 118, 4727-4742.
TransitionPathsof Met-Enkephalin from Markov State Modeling of a Molecular Dynamics Trajectory, Banerjee R. and Cukier R. I., J. Phys. Chem. B 2014, 118, 2883-2895.
ComputationalSimulationStrategiesforAnalysisofMultisubunitRNAPolymerases, Wang B. B., Feig M., Cukier R. I., & Burton Z. F., Chem. Revs. 2013, 113, 8546-8566.
ExcessDielectronin an Ionic Liquid as a Dynamic Bipolaron, Liu J. X., Wang Z. P., Zhang M., Cukier R. I., and Bu Y. X., Phys. Rev. Letts. 2013, 110, 107602.
Variance of a Potential of Mean Force Obtained Using the Weighted Histogram Analysis
Method, Cukier R. I., J.Phys.Chem.B 2013, 117, 14785-14796.
SimulationsofTemperatureandSaltConcentration Effects on bZIP, a Basic Region Leucine Zipper, Cukier R. I., J.Phys.Chem. B 2012, 116, 6071-6086.
A Hamiltonian replica exchange method for building protein-protein interfaces applied
to a leucine zipper, Cukier R. I., J. Chem. Phys. 2011, 134, 045104.
CV
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
