The Turner group has published numerous articles over the years that detail the development of the RNA folding parameters. The closely related ‘RNAstructure’ program has also been described ( 23, 24). The description and use of the mfold package has appeared in a number of articles ( 19– 22). They have minimum free energy conditional on containing the chosen base pair. Base pairs within this free energy increment are chosen either automatically, or else by the user, and foldings that contain the chosen base pair are computed. From this, δδ G is computed to be P/100 |Δ G|. The free energy increment, δδ G, is chosen a priori by the user, who selects a ‘percent suboptimality’, P. The base pair r i− r j is plotted in row i and column j of this matrix. Any base pair, r i− r j, between the ith nucleotide and the jth nucleotide that is contained in a folding no more than δδ G from the minimum, is plotted in a triangular plot called the ‘energy dot plot’. The core algorithm predicts a minimum free energy, Δ G, as well as minimum free energies for foldings that must contain any particular base pair. The ‘mfold’ software for RNA folding was developed in the late 1980s ( 18). Turner, Department of Chemistry, University of Rochester, Rochester, NY) were used ( 17). After 1986, free energies from the Turner group (Doug H. Initially, they used free energy parameters that had been summarized by Salser ( 16). They were popular in the 1980s and a modified version was incorporated into the UWGCG (University of Wisconsin Genetics Computer Group) suite of programs ( 15) the acronym was shortened to GCG when this group left the University of Wisconsin to form a private company. My own early RNA folding programs ( 12, 14) computed a single minimum energy folding of an RNA sequence. Efficient algorithms for RNA secondary structure prediction using dynamic programming methods borrowed from sequence alignment were developed independently by a number of people ( 8– 13). The prediction of RNA secondary structure (folding) by energy minimization using nearest neighbor energy parameters began with Tinoco and colleagues ( 3– 6) and also with Delisi and Crothers ( 7). The concept of RNA secondary structure began with the work of Doty and Fresco ( 1, 2). Received FebruRevised and Accepted ApINTRODUCTION
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