Cyrus Chothia: structural biologist and pioneer in protein evolution

Research and major contributions

Chothia combined structural analysis with evolutionary thinking to show that protein architecture is constrained by function and ancestry. His work demonstrated how structural similarity tends to persist even as amino-acid sequences diverge, and he helped quantify the relationship between sequence identity and structural divergence. These findings underlie modern methods for recognizing evolutionary relationships from sequence data and for modelling protein structures.

He made especially influential contributions to immunology by analysing antibody variable regions. Alongside collaborators, Chothia described recurring loop conformations—so-called "canonical structures"—in complementarity-determining regions (CDRs), providing a framework used in antibody modelling and engineering.

Legacy and impact

• Advanced the concept that a limited number of protein folds recur across biology, influencing structural classification efforts.
• Contributed to databases and classification schemes that organize protein domain structures, enabling comparative studies and computational annotation.
• Provided quantitative foundations for structure prediction, homology modelling and the interpretation of sequence variation in an evolutionary context.

Chothia was elected a Fellow of the Royal Society in recognition of his contributions to molecular biology. Colleagues remember him for clear conceptual advances that bridged detailed structural work and large-scale bioinformatics. He died in November 2019, leaving a lasting influence on how researchers connect sequence, structure and function in proteins.