 Jesse Stombaugh

Jesse Stombaugh has contributed to the geometric analysis of RNA structures. His 2002 paper with Neocles B. Leontis and Eric Westhof classifies noncanonical base pairs and organizes their geometric compatibility in RNA isostericity matrices. The paper's byline associates Stombaugh with Bowling Green State University's chemistry and biomolecular-sciences research.^[ref]

The underlying problem is that nucleotide sequence alone does not specify which edges of two nucleobases contact or how their attached backbones are arranged. A replacement can preserve a contact's geometry while changing its chemical composition. Stombaugh's coauthored classification provides a framework for testing such replacements, rather than treating every base pair with the same two letters as the same structure.

Stombaugh is first author of the 2009 study Frequency and isostericity of RNA base pairs by Jesse Stombaugh and others, with Craig L. Zirbel, Eric Westhof and Neocles B. Leontis. It introduces the RNA IsoDiscrepancy Index and compares geometrically aligned ribosomal RNA structures with sequence variation.^[ref]

An original comparison illustrates the question. The standard cis Watson–Crick A–U and G–C contacts are geometrically compatible, even though they have two and three hydrogen bonds, respectively. Replacing A–U by G–C can therefore preserve the approximate backbone scaffold without preserving every contribution to free energy or recognition by a protein. Conversely, simply reversing the order of a wobble pair need not preserve its geometry. Geometry, contact chemistry and local sequence context must be assessed separately.

These studies combine structural coordinates with comparative analysis; they do not infer a unique three-dimensional fold from a short sequence alone. A correlated substitution can support a structural hypothesis, but actual contacts and model errors still need checking against experimental structures.