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Simple physical models connect theory and experiment in protein folding kinetics.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Alm, Eric John Morozov, Alexandre V. Kortemme, Tanja Baker, David |
| Copyright Year | 2002 |
| Abstract | Our understanding of the principles underlying the protein-folding problem can be tested by developing and characterizing simple models that make predictions which can be compared to experimental data. Here we extend our earlier model of folding free energy landscapes, in which each residue is considered to be either folded as in the native state or completely disordered, by investigating the role of additional factors representing hydrogen bonding and backbone torsion strain, and by using a hybrid between the master equation approach and the simple transition state theory to evaluate kinetics near the free energy barrier in greater detail. Model calculations of folding phi-values are compared to experimental data for 19 proteins, and for more than half of these, experimental data are reproduced with correlation coefficients between r=0.41 and 0.88; calculations of transition state free energy barriers correlate with rates measured for 37 single domain proteins (r=0.69). The model provides insight into the contribution of alternative-folding pathways, the validity of quasi-equilibrium treatments of the folding landscape, and the magnitude of the Arrhenius prefactor for protein folding. Finally, we discuss the limitations of simple native-state-based models, and as a more general test of such models, provide predictions of folding rates and mechanisms for a comprehensive set of over 400 small protein domains of known structure. |
| Starting Page | 491 |
| Ending Page | 500 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.physics.rutgers.edu/~morozov/pdfs/Alm_Morozov_JMB2002.pdf |
| Alternate Webpage(s) | http://depts.washington.edu/bakerpg/drupal/system/files/alm02A.pdf |
| Alternate Webpage(s) | http://depts.washington.edu/bakerpg/papers/12217703.pdf |
| Alternate Webpage(s) | http://depts.washington.edu/bakerpg/papers/Alm-JMB-v322-p463.pdf |
| PubMed reference number | 12217703v1 |
| Volume Number | 322 |
| Issue Number | 2 |
| Journal | Journal of molecular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Greater Than Hydrogen Bonding Kinetics Protein Domain Pyschological Bonding Vertebral column free energy protein folding |
| Content Type | Text |
| Resource Type | Article |