sequencestructurefunction

Sequence-structure-function is a foundational concept in biology describing how the linear sequence of a biomolecule encodes its three-dimensional structure, which in turn determines its biological role. The relationship is complex and context-dependent: small sequence changes can alter folding and activity, while different sequences can sometimes converge on similar structures and functions.

For proteins, the primary sequence of amino acids guides folding into hierarchical levels of structure—secondary, tertiary, and, when present, quaternary assemblies. The arrangement of residues creates folding motifs, domains, binding pockets, and catalytic sites. Function emerges from shape, chemical properties, and dynamics that enable substrate binding, chemical transformation, and interactions with other molecules. Stability, allosteric shifts, and conformational changes often regulate activity.

For nucleic acids, sequence dictates base pairing and the formation of secondary and tertiary structures. RNA, in particular, can fold into stems, loops, pseudoknots, and complex architectures that enable catalysis, regulation, and molecular recognition. DNA primarily stores information, but regulatory DNA and RNA structures can influence transcription, translation, and RNA processing. In both macromolecule families, structure mediates interactions with ligands, proteins, or other nucleic acids.

Predicting structure from sequence is a central goal of bioinformatics and structural biology. Methods include homology modeling, threading, and ab initio approaches for proteins, and energy-based or comparative methods for RNA. Advances in structure prediction, including deep-learning tools, improve inference but function remains tied to the cellular environment, dynamics, and post-translational or post-transcriptional modifications. Understanding sequence-structure-function supports fields from enzyme design to disease genetics and drug discovery.