Biomolecular structure chemical probing, hydroxyl radical probing, nucleotide analog interference mapping (NAIM), and in-line probing. Protein and nucleic acid structures can be determined using either nuclear magnetic resonance spectroscopy (NMR) or X-ray crystallography or single-particle cryo electron microscopy (cryoEM). The first published reports for DNA (by Rosalind Franklin and Raymond Gosling in 1953) of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson function transforms that provided only a limited amount of structural information for oriented fibers of DNA isolated from calf thymus. An alternate analysis was then proposed by Wilkins et al. in 1953 for B-DNA X-ray diffraction and scattering
History of molecular biology modeling efforts of Watson and Crick. In their modeling, Watson and Crick restricted themselves to what they saw as chemically and biologically reasonable. Still, the breadth of possibilities was very wide. A breakthrough occurred in 1952, when Erwin Chargaff visited Cambridge and inspired Crick with a description of experiments Chargaff had published in 1947. Chargaff had observed that the proportions of the four nucleotides vary between one DNA sample and the next, but that for particular pairs of nucleotides — adenine and thymine, guanine and cytosine — the two nucleotides are always present in equal proportions. Using X-ray diffraction, as