Margaret Belle (Oakley) Dayhoff (March 11, 1925 – February 5, 1983) was an American physical chemist and a pioneer in the field of bioinformatics. Dayhoff was a professor at Georgetown University Medical Center and a noted research biochemist at the National Biomedical Research Foundation, where she pioneered the application of mathematics and computational methods to the field of biochemistry.  She dedicated her career to applying the evolving computational technologies to support advances in biology and medicine, most notably the creation of protein and nucleic acid databases and tools to interrogate the databases.  She originated one of the first substitution matrices, point accepted mutations (PAM). The one-letter code used for amino acids was developed by her, reflecting an attempt to reduce the size of the data files used to describe amino acid sequences in an era of punch-card computing.
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.  She did postdoctoral studies at the Rockefeller Institute (now Rockefeller University) and the University of Maryland, and joined the newly established National Biomedical Research Foundation in 1959. She was the first woman to hold office in the Biophysical Society and the first person to serve as both secretary and eventually president.