Abstract
We develop a sequence based α-carbon model to incorporate a mean field estimate of the orientation dependence of the polypeptide chain that gives rise to specific hydrogen bond pairing to stabilize α-helices and β-sheets. We illustrate the success of the new protein model in capturing thermodynamic measures and folding mechanism of proteins L and G. Compared to our previous coarse-grained model, the new model shows greater folding cooperativity and improvements in designability of protein sequences, as well as predicting correct trends for kinetic rates and mechanism for proteins L and G. We believe the model is broadly applicable to other protein folding and protein-protein co-assembly processes, and does not require experimental input beyond the topology description of the native state. Even without tertiary topology information, it can also serve as a mid-resolution protein model for more exhaustive conformational search strategies that can bridge back down to atomic descriptions of the polypeptide chain.
Original language | English (US) |
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Pages (from-to) | 626-638 |
Number of pages | 13 |
Journal | Proteins: Structure, Function and Genetics |
Volume | 70 |
Issue number | 3 |
DOIs | |
State | Published - Feb 15 2008 |
Externally published | Yes |
Keywords
- Anisotropic hydrogen-bonding
- Coarse-grained protein models
- Kinetics
- Multiscale models
- Protein folding
- Simulation
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology