Margaret Belle (Oakley) Dayhoff (March 11, 1925 – February 5, 1983) was an American Biophysicist and a pioneer in the field of bioinformatics.

Her PhD degree was from Columbia University in the department of chemistry, where she devised computational methods to calculate molecular resonance energies of several organic compounds.

[3] Her academic promise was evident from the outset – she was valedictorian (class of 1942) at Bayside High School, Bayside, New York, and from there received a scholarship to Washington Square College of New York University, graduating magna cum laude in mathematics in 1945 and getting elected to Phi Beta Kappa.

In her graduate thesis, Dayhoff pioneered the use of computer capabilities – i.e. mass-data processing – to theoretical chemistry; specifically, she devised a method of applying punched-card business machines to calculate the resonance energies of several polycyclic organic molecules.

[5] At the NBRF, she began to work with Robert Ledley, a dentist who had obtained a degree in physics and become interested in the possibilities of applying computational resources to biomedical problems.

[8] In the early 1960s, Dayhoff also collaborated with Ellis Lippincott and Carl Sagan to develop thermodynamic models of cosmo-chemical systems, including prebiological planetary atmospheres.

To perform this work, she created the single-letter amino acid code to minimize the data file size for each sequence.

In later years, she applied these methods to study a number of molecular relationships, such as the catalytic chain and bovine cyclic AMP-dependent protein kinase and the src gene product of Rous avian and Moloney murine sarcoma viruses; antithrombin-III, alpha-antitrypsin, and ovalbumin; epidermal growth factor and the light chain of coagulation factor X; and apolipoproteins A-I, A-II, C-I and C-III.

Along with a model of indel events, alignments generated by these methods can be used in an iterative process to construct new count matrices until convergence.

The notion that such molecular analysis could help scientists decode evolutionary patterns in organisms was formalized in the published papers of Emile Zuckerkandl and Linus Pauling in 1962 and 1965.

[5] Dayhoff's Atlas became a template for many indispensable tools in large portions of DNA or protein-related biomedical research.

The contract to manage GenBank (a technology directly related to her research), awarded in the early 1980s by the NIH, went to Walter Goad at the Los Alamos National Laboratory.

[19] Despite the success of Dayhoff's Atlas, experimental scientists and researchers considered their sequence information very valuable and were often reluctant to submit it to such a publicly available database.

[20] During the last few years of her life, she focused on obtaining stable, adequate, long-term funding to support the maintenance and further development of her Protein Information Resource.

[3] A fund was established after her death in 1984 to endow the Margaret O. Dayhoff Award, one of the top national honors in biophysics.

[5] David Lipman, director of the National Center for Biotechnology Information, has called Dayhoff the "mother and father of bioinformatics".