Insight into a molecular interaction force supporting peptide backbones and its implication to protein loops and folding

Abstract

Although not being classified as the most fundamental protein structural elements like α-helices and β-strands, the loop segment may play considerable roles for protein stability, flexibility, and dynamic activity. Meanwhile, the protein loop is also quite elusive; i.e. its interactions with the other parts of protein as well as its own shape-maintaining forces have still remained as a puzzle or at least not quite clear yet. Here, we report a molecular force, the so-called polar hydrogen–π interaction (Hp–π), which may play an important role in supporting the backbones of protein loops. By conducting the potential energy surface scanning calculations on the quasi π-plane of peptide bond unit, we have observed the following intriguing phenomena: (1) when the polar hydrogen atom of a peptide unit is perpendicularly pointing to the π-plane of other peptide bond units, a remarkable Hp–π interaction occurs; (2) the interaction is distance and orientation dependent, acting in a broad space, and belonging to the ‘point-to-plane’ one. The molecular force reported here may provide useful interaction concepts and insights into better understanding the loop’s unique stability and flexibility feature, as well as the driving force of the protein global folding.

Keywords:

• protein structures
• secondary structure
• protein loops
• Hp–π interaction
• hydrogen bond

Acknowledgements

The authors wish to thank the three anonymous reviewers, whose constructive comments are very helpful for strengthening the presentation of this paper. We thank the National Supercomputer Center (NSCC www.nscc-tj.gov.cn) in Tianjin for the valuable help in the calculations using TH-1A super computer.

Additional information

Funding

This work was supported by grant from the National Science Foundation of China (NSFC http://www.nsfc.gov.cn/) under the contract numbers 31370716 and 31360207.