Shaping up the protein folding funnel by local interaction: Lesson from a structure prediction study
Open Access
- 17 February 2006
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 103 (9), 3141-3146
- https://doi.org/10.1073/pnas.0508195103
Abstract
Predicting protein tertiary structure by folding-like simulations is one of the most stringent tests of how much we understand the principle of protein folding. Currently, the most successful method for folding-based structure prediction is the fragment assembly (FA) method. Here, we address why the FA method is so successful and its lesson for the folding problem. To do so, using the FA method, we designed a structure prediction test of “chimera proteins.” In the chimera proteins, local structural preference is specific to the target sequences, whereas nonlocal interactions are only sequence-independent compaction forces. We find that these chimera proteins can find the native folds of the intact sequences with high probability indicating dominant roles of the local interactions. We further explore roles of local structural preference by exact calculation of the HP lattice model of proteins. From these results, we suggest principles of protein folding: For small proteins, compact structures that are fully compatible with local structural preference are few, one of which is the native fold. These local biases shape up the funnel-like energy landscape.Keywords
This publication has 58 references indexed in Scilit:
- Improved Gō-like Models Demonstrate the Robustness of Protein Folding Mechanisms Towards Non-native InteractionsJournal of Molecular Biology, 2003
- Roles of native topology and chain-length scaling in protein folding: A simulation study with a Gō-like modelJournal of Molecular Biology, 2001
- Ab Initio Protein Structure Prediction: Progress and ProspectsAnnual Review of Biophysics and Biophysical Chemistry, 2001
- Is the Unfolded State the Rosetta Stone of the Protein Folding Problem?Biochemical and Biophysical Research Communications, 2000
- Topological and energetic factors: what determines the structural details of the transition state ensemble and “en-route” intermediates for protein folding? an investigation for small globular proteinsJournal of Molecular Biology, 2000
- Free energy landscapes of peptides by enhanced conformational sampling 1 1Edited by B. HonigJournal of Molecular Biology, 2000
- Prediction and structural characterization of an independently folding substructure in the src SH3 domainJournal of Molecular Biology, 1998
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and bayesian scoring functionsJournal of Molecular Biology, 1997
- Accurate modeling of protein conformation by automatic segment matchingJournal of Molecular Biology, 1992