Office: 4335 GBSF
Telephone: (530) 754 7632
Ph.D., Physics, University of Pittsburgh, 1996
M.S., Physics (NMR), Wuhan Institute of Physics and Mathematics, Academia Sinica, P.R. China
B.S., Physics, Wuhan University, China
Our main research interests are development and application of computational methods to study the structure and dynamics of bio-molecular systems. We focus on protein folding and aggregation and protein structure prediction, simulation method development, structure and dynamics of G-protein coupled receptors, DNA-protein interactions, and computer aided drug design.
Proteins need to “fold” to their native productive states to become biologically active. A number of proteins can also misfold and have been linked to a number of human diseases, including cystic fibrosis, Alzheimer’s disease and other amyloidoses, and prion spongiform encephalopathies such as Creutzfeldt-Jacob disease. An understanding of the mechanism differentiating productive protein folding from misfolding and aggregation is critical to preventing misfolding and misassembly of proteins and would enable us to predict protein structures more accurately and to design new proteins. We are conducting simulation studies to elucidate the process of protein folding and aggregation.
G-protein coupled receptors (GPCR) are membrane proteins that can be activated/deactivated by external stimuli and initiate signal transduction. GPCR have been the premier targets of drug development effort and about 50% of the existing drugs on the market are designed to interact with GPCRs. GPCRs are believed to share a common 7 transmembrane architecture with relatively flexible extra-cellular and cytoplasmic domains. Therefore, computational modeling can play important role to provide detailed and accurate information on the structure and dynamics of GPCRs.
The interactions between proteins and DNA play a central role in molecular biology and genomics. These interactions include both sequence-specific and sequence-non-specific types. In the sequence-specific interactions, proteins recognize a specific DNA sequence (e.g., restriction enzymes and transcription factors). In the non-specific type, proteins interact with DNA regardless of the sequence. These interactions are crucial for gene expression, gene activation/repression. Thus, understanding these interactions is considered a key step toward functional interpretation of genetic sequences in the post-genomic era.
Last updated 5/21/2010
H. Lei, C. Wu, Z.-X. Wang and Y. Duan (2006) “Molecular dynamics simulations and free energy analyses on the dimer formation of an amyloidogenic heptamer peptide from human beta2-microglobulin: implication to the protofibril structure”, J. Mol. Biol. 356(4), 1049-1063
H. Lei, C. Wu, H. Liu, and Y. Duan (2007) “Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations”, PNAS, 104(12), 4925-4930
T. Wang and Y. Duan (2007) “Chromophore Channeling in the G-Protein Coupled Receptor Rhodopsin”, J. Am. Chem. Soc. (Communication), 129(22), 6970-6971
W. Zhang and Y. Duan (2006) “Grow to Fit Molecular Dynamics (G2FMD): an ab initio method for protein side chain assignment and refinement” Protein Engineering, Design and Selection 19: 55-65;
C. Wu, H. Lei and Y. Duan (2005) “Elongation of Ordered Peptide Aggregate of an Amyloidogenic Hexapeptide (NFGAIL) Observed in Molecular Dynamics Simulations with Explicit Solvent”, J. Am. Chem. Soc. 127(39), 13530-13537
H.X. Lei and Y. Duan (2007) “Two-stage folding of HP-35 from ab initio simulations”, JMB, 370(1), 196-206(cover story)
A. J. Fischer, N. C. Rockwell, A. Y. Jang, L. A. Ernst, A. S. Waggoner,Y. Duan, H. Lei, and J. C. Lagarias, (2005) “Multiple Roles of a Conserved GAF Domain Tyrosine Residue in Cyanobacterial and Plant Phytochromes”, Biochemistry 44(46), 15203-15215
W. Zhang, C. Wu, and Y. Duan (2005) “Convergence of replica exchange molecular dynamics”, J. Chem. Phys., 123(15), 154105
M. C. Lee, R. Yang, and Y. Duan, (2005) “Comparison between Generalized-Born and Poisson-Boltzmann methods in Physics Based Scoring Functions for Protein Structure Prediction”J. Mol. Mod. 12, 101-110
R. Yang, M. C. Lee, H. Yan, and Y. Duan, (2005) Loop Conformation and Dynamics of the E. coli HPPK Apo-enzyme and Its Binary Complex with MgATP, Biophys. J., 89(1): 95-106.
M. C. Lee, J. Deng, J. M. Briggs and Y. Duan, (2005) Large Scale Conformational Dynamics of the HIV-1 Integrase Core Domain and its Catalytic Loop Mutants, Biophys. J., 88: 3133-3146
Wu, C., H. Lei, and Y. Duan, (2005)The role of Phe in the formation of well-ordered oligomers of amyloidogenic hexapeptide (NFGAIL) observed in molecular dynamics simulations with ex-plicit solvent. Biophys. J. 88(4): 2897-2906
J. N. Sarakatsannis and Y. Duan, (2005) Statistical characterization of salt bridges in proteins, Proteins, 60(4), 732-739
Chowdhury, H.X. Lei and Y. Duan, (2005) Denatured state ensemble and early stage of folding of the G29A Mutant of B-domain of protein A: An all atom molecular dynamics study, J. Phys. Chem., B, 109, 9073-9081
Wu, C., H.X. Lei, and Y. Duan, (2004)Formation of partially ordered oligomers of amyloido-genic hexapeptide (NFGAIL) in aqueous solution observed in molecular dynamics simulations. Biophys. J., 87(5): p. 3000-3009
Lei, H.X. and Y. Duan, (2004) The role of plastic beta-hairpin and weak hydrophobic core in the stability and unfolding of a full sequence design protein. J. Chem. Phys., 121(23): p. 12104-12111
Lei, H. and Y. Duan, (2004). “Incorporating intermolecular distance into protein-protein dock-ing”. Prot. Eng., 17(12): p. 837-845
Wang, Z.X. and Y. Duan, (2004) Solvation effects on alanine dipeptide: A MP2/cc-pVTZ//MP2/6-31G** study of (Phi, Psi) energy maps and conformers in the gas phase, ether, and water. J. Comp. Chem., 25(14): p. 1699-1716
W. Zhang, H. Lei, S. Chowdhury and Y. Duan (2004) Fs-21 peptides can form both single helix and helix-turn-helix, J. Phys. Chem., 108(22): p. 7479-7489
M. C. Lee and Y. Duan, (2004) Distinguish Protein Decoys Using a Scoring Function Based on AMBER Force Field, Short Molecular Dynamics Simulations and the Generalized Born Solvent Model, Proteins, 2004. 55(3): p. 620-634
Y. Duan, C. Wu, S. Chowdhury, M. C. Lee, G. Xiong, W. Zhang, R. Yang, P. Cieplak, R. Luo, T. Lee, J. Caldwell, J. Wang, and P. A. Kollman (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechani-cal calculations, J. Comp. Chem., 24(16) 1999-2012.
S. Chowdhury, M. Lee, G. Xiong, and Y. Duan, (2003) ab initio folding simulation of the Trp-cage mini-protein approaches NMR resolution, J. Mol. Biol., 327: (3) 711 – 717
Duan, Y. and P. A. Kollman, (1998) Pathways to a protein folding intermediate observed in a 1-ms simulation in aqueous solution, Science, 282, 740-744