The role of atomic level steric effects and attractive forces in protein folding
Heiko Lammert
Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093
Search for more papers by this authorPeter G. Wolynes
Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093
Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005-1827
Search for more papers by this authorCorresponding Author
José N. Onuchic
Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093
Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005-1827
Center for Theoretical Biological Physics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0374===Search for more papers by this authorHeiko Lammert
Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093
Search for more papers by this authorPeter G. Wolynes
Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093
Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005-1827
Search for more papers by this authorCorresponding Author
José N. Onuchic
Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093
Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005-1827
Center for Theoretical Biological Physics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0374===Search for more papers by this authorAbstract
Protein folding into tertiary structures is controlled by an interplay of attractive contact interactions and steric effects. We investigate the balance between these contributions using structure-based models using an all-atom representation of the structure combined with a coarse-grained contact potential. Tertiary contact interactions between atoms are collected into a single broad attractive well between the Cβ atoms between each residue pair in a native contact. Through the width of these contact potentials we control their tolerance for deviations from the ideal structure and the spatial range of attractive interactions. In the compact native state dominant packing constraints limit the effects of a coarse-grained contact potential. During folding, however, the broad attractive potentials allow an early collapse that starts before the native local structure is completely adopted. As a consequence the folding transition is broadened and the free energy barrier is decreased. Eventually two-state folding behavior is lost completely for systems with very broad attractive potentials. The stabilization of native-like residue interactions in non-perfect geometries early in the folding process frequently leads to structural traps. Global mirror images are a notable example. These traps are penalized by the details of the repulsive interactions only after further collapse. Successful folding to the native state requires simultaneous guidance from both attractive and repulsive interactions. Proteins 2012. © 2011 Wiley Periodicals, Inc.
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