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Eric Westhof is a structural biochemist whose research concerns the architecture and molecular interactions of RNA. His institutionally hosted CV identifies work at Strasbourg's IBMC and a professorship in structural biochemistry.^[ref]

With N. B. Leontis, Westhof developed a geometric nomenclature for RNA base-pair geometry. The classification records the interacting RNA base-pair edges and the relative orientations of the two glycosidic bonds, allowing noncanonical base pairs to be described systematically.^[ref]

An important distinction is between two kinds of orientation. The glycosidic torsion angle $\chi$ describes how one base rotates relative to its own sugar, giving syn glycosidic conformation or anti glycosidic conformation. The pair's cis/trans descriptor instead relates the two glycosidic bonds across the base-pair interaction. Reporting one descriptor does not automatically report the other.

A geometric family also leaves room for different base identities. The question of RNA base-pair isostericity is whether substitutions can preserve the relevant relative placement and shape sufficiently to support a similar structural role. This makes geometry useful when comparing homologous RNA structures even when their sequences differ.^[ref]

Westhof's contribution helped connect structural observations with a reusable language for comparing RNA folds, rather than restricting descriptions to the familiar sequence letters or canonical base pairs.

Neocles B. Leontis studied RNA structure and molecular recognition at Bowling Green State University. His institutional profile identifies him as a chemistry professor and biology adjunct working on nucleic acids.^[ref]

With E. Westhof, Leontis proposed a systematic classification of RNA base-pair geometry using three possible interacting RNA base-pair edges and two relative glycosidic-bond orientations.^[ref]

A small counting argument explains the12basic families. Write $W,H,S$ for the Watson–Crick, Hoogsteen and Sugar edges. Treating interchange of the two bases as the same edge-family givesThere are6unordered choices with repetition. Each can have cis or trans relative glycosidic-bond orientation, giving $6\times 2=12$. This counts geometric families, not nucleotide sequences or the number of hydrogen bonds in every individual interaction.

The classification provides a way to annotate noncanonical base pairs and compare structural motifs. The2001 paper also explains how geometric families can reveal RNA base-pair isostericity, connecting observed structures to plausible substitutions in related sequences.^[ref]

An RNA base-pair edge is a region around a nucleobase presenting groups that can participate in an edge-to-edge contact with another nucleobase. It is a chemical contact surface in RNA base-pair geometry, rather than an edge of a drawn secondary-structure graph. The arrangement of hydrogen bond donors and hydrogen bond acceptors constrains possible partners.

The Leontis–Westhof classification distinguishes the Watson-Crick base-pair edge, Hoogsteen base-pair edge and sugar base-pair edge. The last category includes the ribose $2^{\prime }$-hydroxyl contribution and is also called the shallow-groove edge in the original classification.^[ref] Thus an edge label does not necessarily refer only to atoms in the aromatic ring.

An edge belongs to one partner. A complete pair description identifies the edge used by each nucleobase and the relative orientation of their glycosidic bonds. For example, specifying that one adenine uses its Hoogsteen base-pair edge still leaves the second partner's identity, contacting edge and orientation to be determined. It does not by itself specify a unique noncanonical base pair.

For an original classification exercise, label two partners A and B. The record “A uses Watson–Crick; B uses sugar; orientation trans” contains more geometric information than “A contacts B”. Exchanging the names A and B reverses the written edge order but does not create a second physical contact. In contrast, moving B to a different contact surface changes the proposed structure.

Structural coordinates or solution restraints are needed to establish the contact. A plausible hydrogen bond donor near an appropriate hydrogen bond acceptor is a necessary geometric clue, not proof that a proposed RNA structure is populated under every condition. Edge labels make comparisons precise while retaining the need for experimental evidence.

RNA base-pair geometry specifies how two nucleobases contact and orient relative to one another, beyond their letter identities. It distinguishes different base pairing arrangements, including noncanonical base pairs, that can organize RNA secondary structure and three-dimensional folding.

A primary classification uses the contacting RNA base-pair edge of each partner: Watson–Crick, Hoogsteen or sugar edge. It also distinguishes cis and trans orientations of the two glycosidic bonds relative to the interbase hydrogen bonds. These are pairwise geometric descriptors; they are not simply labels for parallel versus antiparallel nucleic acid strands.^[ref]

An original counting explanation clarifies the twelve basic families. Ignoring exchange of the two partner labels, three edge types allow three same-edge combinations and three mixed-edge combinations: six possibilities. Combining each with cis or trans orientation gives $6\times 2=12$. This counts contact-geometry families, not twelve possible nucleotide sequences or twelve equally common structures.

For example, knowing only that a contact is guanine–adenine does not specify which RNA base-pair edges participate. Replacing that pair by another two-base combination also does not guarantee the new contact fits the same surrounding backbone. Geometry can therefore explain why one sequence substitution preserves a structural motif while another disrupts it. The classification was designed to support structural comparison and recognition of geometrically similar pairs.^[ref]

Experimental coordinates or solution restraints are needed to assign an actual contact. A proposed hydrogen bond requires a compatible arrangement of donor and acceptor groups, not merely a favorable pair of letters. A secondary-structure arc records a relationship between residues; a full RNA base-pair geometry adds spatial information that the arc alone cannot encode.

RNA base-pair isostericity is geometric similarity between base pairs that allows one pairing arrangement to replace another while approximately preserving the positions and orientations of the attached sugar–phosphate backbones. The important comparisons include the separation of the two ribose $\mathrm{C}{1}^{\prime }$ atoms and the relative directions of the glycosidic bonds. The bases need not have identical chemical composition or occupy exactly the same volume.^[ref]

A useful example is the canonical cis Watson–Crick family. Its adenine–uracil, uracil–adenine, guanine–cytosine and cytosine–guanine pairs belong to the same isosteric subgroup in the primary classification. Thus a paired sequence substitution can exchange an A–U contact for G–C while approximately retaining the local backbone geometry.^[ref]

An original comparison makes the limit clear. The canonical A–U contact has two hydrogen bonds, while G–C has three. Their geometric compatibility does not assert identical free energy, identical base stacking with neighboring residues, or identical recognition by a bound protein. A substitution can preserve the local scaffold while changing other physical properties.

Likewise, sharing a broad RNA base-pair geometry does not guarantee isostericity. The family identifies the two contacting RNA base-pair edges and the cis/trans relationship of the glycosidic bonds. Within a family, different base combinations can still place the ribose attachment points at different separations. An RNA isostericity matrix groups combinations into the more restrictive compatible subsets.^[ref]

The classification is grounded in structures rather than sequence names alone. The primary survey inspected coordinate models from X-ray crystallography, recording structure identifiers, resolution and ribose-attachment separation, and distinguished observed examples from modeled contacts. This supplies a way to test an annotation against actual atomic geometry.^[ref]

For comparative sequence analysis, correlated changes at two positions are therefore evidence to evaluate against a proposed contact geometry. They do not prove by themselves that the residues contact one another. Conversely, a conserved geometric interaction can survive substantial changes in nucleotide sequence, helping explain how similar RNA folds can use different base identities.

The sugar base-pair edge is the side of a nucleobase adjoining its ribose attachment region, including the ribose $2^{\prime }$-hydroxyl group when it participates in the contact. It is one of the three RNA base-pair edges used to classify RNA base-pair geometry. The original nomenclature also calls it the shallow-groove edge.^[ref]

This definition deliberately extends beyond the base ring. In the usual anti orientation about the glycosidic bond, the ribose $2^{\prime }$-hydroxyl can act as a hydrogen bond donor or hydrogen bond acceptor in the pairing interaction. Some sugar-edge contacts therefore connect a base to its partner's ribose rather than consisting solely of direct base-to-base hydrogen bonds.^[ref]

For an original annotation example, suppose residue 1 contributes its $2^{\prime }$-hydroxyl to an inter-residue hydrogen bond. Recording only the two aromatic base rings would omit that contact. A full record must identify the ribose atom, its partner and the geometry. Calling the interaction sugar-edge does not mean that an additional sugar molecule has joined the RNA; the group belongs to an existing nucleotide.

A complete pair description still needs the other partner's edge and the cis/trans relationship of the two glycosidic bonds. Sugar–sugar and Watson–Crick–sugar contacts are different families. The words “sugar edge” alone do not specify a unique pair of bases or a unique three-dimensional arrangement.

There is also an experimental limitation. The primary structural survey did not infer the $2^{\prime }$-hydroxyl hydrogen's exact position from the available X-ray crystallography coordinates. It represented the group as a unit and used compatible heavy-atom geometry to discuss possible hydrogen bonds. A close oxygen contact is evidence to interpret with donor/acceptor chemistry, not direct observation of the hydrogen's orientation.^[ref]

This distinction is useful when comparing RNA with a modified backbone: removing or replacing a ribose group can change a contact opportunity without changing the attached nucleobase's letter. Whether the whole fold survives that alteration remains a structural and experimental question.