Geometrical model for the native-state folds of proteins.
We recently introduced a physical model [T.X. Hoang, A. Trovato, F. Seno, J.R. Banavar, A. Maritan, Geometry and symmetry pre-sculpt the free energy landscape of proteins. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 7960-7964, J.R. Banavar, T.X. Hoang, A. Maritan, F. Seno, A. Trovato, A unified perspective on proteins-a physics approach. Phys. Rev., E 70 (2004) 041905] for proteins which incorporates, in an approximate manner, several key features such as the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and the role played by hydrophobicity. Within this framework, marginally compact conformations resembling the native state folds of proteins emerge as broad competing minima in the free energy landscape even for a homopolymer. Here we show how the introduction of sequence heterogeneity using a simple scheme of just two types of amino acids, hydrophobic (H) and polar (P), and sequence design allows a selected putative native fold to become the free energy minimum at low temperature. The folding transition exhibits thermodynamic cooperativity, if one neglects the degeneracy between two different low energy conformations sharing the same fold topology.
Trinh
X Hoang
XH
Institute of Physics and Electronics, VAST, 10 Dao, Tan, Hanoi, Vietnam.
Trovato
Antonio
A
Seno
Flavio
F
Banavar
Jayanth R
JR
Maritan
Amos
A
D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics
D011108:Polymers; D011506:Proteins