The limited role of non-native contacts in folding pathways of a lattice protein
| Autor: | Juan P. Garrahan, Phillip L. Geissler, Brian C. Gin |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Physics
Protein Folding Sequence design Statistical Mechanics (cond-mat.stat-mech) media_common.quotation_subject Frustration FOS: Physical sciences Transit time Biomolecules (q-bio.BM) Cytoskeletal Proteins Quantitative Biology - Biomolecules Models Chemical Structural Biology FOS: Biological sciences Lattice protein Native state Computer Simulation Protein folding Statistical physics Molecular Biology Native contact Native structure Condensed Matter - Statistical Mechanics Protein Binding media_common |
| DOI: | 10.48550/arxiv.0808.2231 |
| Popis: | Models of protein energetics which neglect interactions between amino acids that are not adjacent in the native state, such as the Go model, encode or underlie many influential ideas on protein folding. Implicit in this simplification is a crucial assumption that has never been critically evaluated in a broad context: Detailed mechanisms of protein folding are not biased by non-native contacts, typically imagined as a consequence of sequence design and/or topology. Here we present, using computer simulations of a well-studied lattice heteropolymer model, the first systematic test of this oft-assumed correspondence over the statistically significant range of hundreds of thousands of amino acid sequences, and a concomitantly diverse set of folding pathways. Enabled by a novel means of fingerprinting folding trajectories, our study reveals a profound insensitivity of the order in which native contacts accumulate to the omission of non-native interactions. Contrary to conventional thinking, this robustness does not arise from topological restrictions and does not depend on folding rate. We find instead that the crucial factor in discriminating among topological pathways is the heterogeneity of native contact energies. Our results challenge conventional thinking on the relationship between sequence design and free energy landscapes for protein folding, and help justify the widespread use of Go-like models to scrutinize detailed folding mechanisms of real proteins. Comment: 11 pages, 4 figures |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|