Exploring the Interplay between Topology and Secondary Structural Formation in the Protein Folding Problem

• Published in: The journal of physical chemistry. B Vol. 107; no. 40; pp. 11193 - 11200
• Main Authors: Cheung, Margaret S, Finke, John M, Callahan, Benjamin, Onuchic, José N
• Format: Journal Article
• Language: English
• Published: American Chemical Society 09.10.2003
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp034441r

Simple models with a single bead representation (Cα models) have been successful in providing a qualitative understanding of the folding mechanism of small globular proteins. Can we go beyond this qualitative understanding and make more detailed quantitative connections to experiments? To achieve this goal, a tractable framework of protein representations whose complexity falls between Cα and all-atom representations is needed to address different energetic competing factors during folding events. Such a model conserves the low computational expense inherent in minimalist models while enhancing the understanding of side-chain packing not existent in simple Cα models. In this work, we present a minimalist representation of protein structures that are used to investigate the competition between native side-chain contacts and nonspecific backbone hydrogen bonds. Our results suggest that native tertiary contacts and dihedrals force the nonspecific hydrogen bonds to adopt native configurations and retain a funneled landscape. In addition, the use of an angular component in the hydrogen bond interaction prevents non-native conformations.