Improving RNA nearest neighbor parameters for helices by going beyond the two-state model

Aleksandar Spasic, Kyle D. Berger, Jonathan L. Chen, Matthew G. Seetin, Douglas H. Turner, David H. Mathews

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

RNA folding free energy change nearest neighbor parameters are widely used to predict folding stabilities of secondary structures. They were determined by linear regression to datasets of optical melting experiments on small model systems. Traditionally, the optical melting experiments are analyzed assuming a two-state model, i.e. a structure is either complete or denatured. Experimental evidence, however, shows that structures exist in an ensemble of conformations. Partition functions calculated with existing nearest neighbor parameters predict that secondary structures can be partially denatured, which also directly conflicts with the two-state model. Here, a new approach for determining RNA nearest neighbor parameters is presented. Available optical melting data for 34 Watson-Crick helices were fit directly to a partition function model that allows an ensemble of conformations. Fitting parameters were the enthalpy and entropy changes for helix initiation, terminal AU pairs, stacks of Watson-Crick pairs and disordered internal loops. The resulting set of nearest neighbor parameters shows a 38.5% improvement in the sum of residuals in fitting the experimental melting curves compared to the current literature set.

Original languageEnglish
Pages (from-to)4883-4892
Number of pages10
JournalNucleic Acids Research
Volume46
Issue number10
DOIs
StatePublished - 1 Jun 2018
Externally publishedYes

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