Natalia's initial interest was in the structure of collagen and related polymers; but by the beginning of 1960s, she initiated crystallographic studies of pepsin that she continued, in one form or another, for the rest of her life. At that time, only a few laboratories in the world and none in the Soviet Union were engaged in the new and exciting field of protein crystallography. Indeed, the total number of protein structures available in 1962 could be counted on the fingers of one hand, and each took a team of scientists many years to solve. Successful crystallographic laboratories in Great Britain and the United States were equipped with powerful rotating anode X-ray sources, and full access to the scientific literature was taken for granted. That was clearly not the case in the USSR of that era, where equipment was hard to get, foreign travel was rare and scientific journals were largely unavailable. However, Natalia was undaunted by those difficulties, which were compounded by the fact that she never engaged in any political activities that could have helped her in reaching her goals. Her laboratory was always underequipped, but she compensated by attracting a number of very talented students, many of whom are now continuing their scientific work in leading institutions throughout the world.

Pepsin was the first aspartic protease to be crystallized (hexagonal crystals were grown in Uppsala in the early 1930s), but solving its structure turned out to be a very difficult task. Although a low-resolution structure of a different crystal form was reported by Natalia and her colleagues in 1970 (ref. 1), it was not until 1976 that major breakthroughs in structural investigations of other aspartic proteases were reported by several groups during the first conference on that subject, organized by Jordan Tang in Norman, Oklahoma. High-resolution structures of three fungal enzymes solved by various laboratories were subsequently used for completing the structure of pepsin2 and correcting some of its aspects3. The structure was finally refined through collaboration between Natalia and the laboratory of Michael James in Edmonton4.

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