title: A kMC-MD method with generalized move-sets for the simulation of folding of α-helical and β-stranded peptides.
abstract: In Monte-Carlo simulations of protein folding, pathways and folding times depend on the appropriate choice of the Monte-Carlo move or process path. We developed a generalized set of process paths for a hybrid kinetic Monte Carlo-Molecular dynamics algorithm, which makes use of a novel constant time-update and allows formation of α-helical and β-stranded secondary structures. We apply our new algorithm to the folding of 3 different proteins: TrpCage, GB1, and TrpZip4. All three systems are seen to fold within the range of the experimental folding times. For the β-hairpins, we observe that loop formation is the rate-determining process followed by collapse and formation of the native core. Cluster analysis of both peptides reveals that GB1 folds with equal likelihood along a zipper or a hydrophobic collapse mechanism, while TrpZip4 follows primarily a zipper pathway. The difference observed in the folding behavior of the two proteins can be attributed to the different arrangements of their hydrophobic core, strongly packed, and dry in case of TrpZip4, and partially hydrated in the case of GB1.
authors: Faculty of Informatics, Institute of Computational Science, University of Lugano, Lugano, Switzerland.
authors: Emanuel K
authors: EK
authors: Peter
authors: Faculty of Informatics, Institute of Computational Science, University of Lugano, Lugano, Switzerland.
authors: Igor V
authors: IV
authors: Pivkin
authors: Department of Chemistry and Biochemistry, and Department of Physics, University of California, Santa Barbara, California 93106, USA.
authors: Joan-Emma
authors: JE
authors: Shea
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides