Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 357, Issue 3, Pages 986-996Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2005.11.074
Keywords
protein folding; topological frustration; modified multicanonical method; IL-1 beta; b-trefoil
Categories
Funding
- NIGMS NIH HHS [GM54038, 1-F31-GM070412-01, R01 GM054038] Funding Source: Medline
Ask authors/readers for more resources
The cytokine, iriterleukin-1 beta (IL-1 beta), adopts a beta-trefoil fold. It is known to be much slower folding than similarly sized proteins, despite having a low contact order. Proteins are sufficiently well designed that their folding is not dominated by local energetic traps. Therefore, protein models that encode only the folded structure and are energetically unfrustrated (GO-type), can capture the essentials of the folding routes. We investigate the folding thermodynamics of IL-1 beta using such a model and molecular dynamics (MD) simulations. We develop an enhanced sampling technique (a modified multicanonical method) to overcome the sampling problem caused by the slow folding. We find that IL-1 beta has a broad and high free energy barrier. In addition, the protein fold causes intermediate unfolding and refolding of some native contacts within the protein along the folding trajectory. This backtracking occurs around the barrier region. Complex folds like the beta-trefoil fold and functional loops like the beta-bulge of IL-1 beta can make some of the configuration space unavailable to the protein and cause topological frustration. (c) 2005 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available