Dr Cyrus Chothia was a preeminent scientist whose pioneering work fundamentally transformed our understanding of protein structure and evolution. He served as an emeritus scientist at the Medical Research Council Laboratory of Molecular Biology at the University of Cambridge and as an emeritus fellow of Wolfson College, Cambridge, where he established himself as a world leader in structural bioinformatics. Following his PhD, he conducted postdoctoral research at the Laboratory of Molecular Biology before working with Michael Levitt at the Weizmann Institute of Science and Joel Janin at the Institut Pasteur in Paris. In 1976, he returned to England to work at University College London and the LMB, where he developed foundational frameworks that would define protein structure classification for decades to come.
Chothia's most significant contribution was the development of the Structural Classification of Proteins (SCOP) database, which he created with Alexey Murzin, Steven Brenner and Tim Hubbard as a comprehensive system for organizing protein structures. In 1992, he proposed that most proteins are built from domains belonging to a limited number of families, revolutionizing how scientists understand protein evolution. His work with Arthur Lesk demonstrated how proteins adapt to mutations through structural changes, while his research with Julian Gough led to the creation of the SUPERFAMILY database using Hidden Markov models to identify protein sequences related to known structures. These innovative resources became indispensable tools for researchers worldwide, providing the foundation for countless discoveries in molecular biology and drug design through their systematic classification of protein architecture.
Elected a Fellow of the Royal Society in 2000, Chothia's work was recognized for showing how amino acid sequences determine protein structure, function and evolution, with his citation noting his development of a protein structure classification now in general use. He received the 2015 ISCB Accomplishment by a Senior Scientist Award for his foundational role in establishing structural bioinformatics as a discipline. Beyond his database creations, Chothia made significant contributions to antibody research, introducing the Chothia numbering scheme and definitions of structural loops that remain standard in the field. His work on the relationship between sequence divergence and structural divergence supported the development of homology modeling methods, which continue to be essential for protein structure prediction. Though he passed away in 2019, Chothia's classification systems continue to guide research in molecular biology, with his work on the correlation between protein superfamilies and organismal complexity offering enduring insights into biological evolution.
