title: Understanding the folding and stability of a zinc finger-based full sequence design protein with replica exchange molecular dynamics simulations.
abstract: Full sequence design protein FSD-1 is a designed protein based on the motif of zinc finger protein. In this work, its folding mechanism and thermal stability are investigated using the replica exchange molecular dynamics model with the water molecules being treated explicitly. The results show that the folding of the FSD-1 is initiated by the hydrophobic collapse, which is accompanied with the formation of the C-terminal alpha-helix. Then the folding proceeds with the formation of the beta-hairpin and the further package of the hydrophobic core. Compared with the beta-hairpin, the alpha-helix has much higher stability. It is also found that the N-capping motif adopted by the FSD-1 contributes to the stability of the alpha-helix dramatically. The hydrophobic contacts made by the side chain of Tyr3 in the native state are essential for the stabilization of the beta-hairpin. It is also found that the folding of the N-terminal beta-hairpin and the C-terminal alpha-helix exhibits weak cooperativity, which is consistent with the experimental data. Meanwhile, the folding pathway is compared between the FSD-1 and the target zinc finger peptide, and the possible role of the zinc ion on the folding pathway of zinc finger is proposed. Proteins 2007. (c) 2007 Wiley-Liss, Inc.
authors.affiliation: National laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing 210093, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D015195:Drug Design; D006358:Hot Temperature; D008958:Models, Molecular; D009038:Motion; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; C108466:FSD-1 protein, synthetic; D014157:Transcription Factors; D015032:Zinc