Modeling peptide nucleic acid binding enthalpies using MM-GBSA

Goodman, Jack; Attwood, David; Kiely, Janice; Coladas Mato, Pablo; Luxton, Richard

Abstract

The binding enthalpies of peptide nucleic acid (PNA) homoduplexes were predicted using a molecular mechanics generalized Born surface area approach. Using the nucleic acid nearest-neighbor model, these were decomposed into sequence parameters which could replicate the enthalpies from thermal melting experiments with a mean error of 8.7%. These results present the first systematic computational investigation into the relationship between sequence and binding energy for PNA homoduplexes and identified a stabilizing helix initiation enthalpy not observed for nucleic acids with phosphoribose backbones.

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2022
• Online Publication Date: Nov 14, 2022
• Publication Date: Nov 24, 2022
• Deposit Date: Dec 1, 2022
• Publicly Available Date: Dec 1, 2022
• Journal: Journal of Physical Chemistry B
• Print ISSN: 1520-6106
• Electronic ISSN: 1520-5207
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 126
• Issue: 46
• Pages: 9528-9538
• DOI: https://doi.org/10.1021/acs.jpcb.2c05547
• Keywords: Binding energy, Enthalpy, Entropy, Free energy, Melting
• Public URL: https://uwe-repository.worktribe.com/output/10192167
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.jpcb.2c05547