Goro Terai1, Satoshi Kamegai1, Kiyoshi Asai2. 1. National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan, INTEC Inc., Koto-ku, Tokyo 136-8637, Japan and. 2. National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8562, Japan.
Abstract
MOTIVATION: An important problem in synthetic biology is to design a nucleotide sequence of an mRNA that confers a desirable expression level of a target protein. The secondary structure of protein-coding sequences (CDSs) is one potential factor that could have both positive and negative effects on protein production. To elucidate the role of secondary structure in CDSs, algorithms for manipulating secondary structure should be developed. RESULTS: We developed an algorithm for designing a CDS with the most stable secondary structure among all possible ones translated into the same protein, and implemented it as the program CDSfold. The algorithm runs the Zuker algorithm under the constraint of a given amino acid sequence. The time and space complexity is O(L(3)) and O(L(2)), respectively, where L is the length of the CDS to be designed. Although our algorithm is slower than the original Zuker algorithm, it could design a relatively long (2.7-kb) CDS in approximately 1 h. AVAILABILITY AND IMPLEMENTATION: The CDSfold program is freely available for non-commercial users as stand-alone and web-based software from http://cdsfold.trahed.jp/cdsfold/ CONTACTS: terai-goro@aist.go.jp or asai@k.u-tokyo.ac.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: An important problem in synthetic biology is to design a nucleotide sequence of an mRNA that confers a desirable expression level of a target protein. The secondary structure of protein-coding sequences (CDSs) is one potential factor that could have both positive and negative effects on protein production. To elucidate the role of secondary structure in CDSs, algorithms for manipulating secondary structure should be developed. RESULTS: We developed an algorithm for designing a CDS with the most stable secondary structure among all possible ones translated into the same protein, and implemented it as the program CDSfold. The algorithm runs the Zuker algorithm under the constraint of a given amino acid sequence. The time and space complexity is O(L(3)) and O(L(2)), respectively, where L is the length of the CDS to be designed. Although our algorithm is slower than the original Zuker algorithm, it could design a relatively long (2.7-kb) CDS in approximately 1 h. AVAILABILITY AND IMPLEMENTATION: The CDSfold program is freely available for non-commercial users as stand-alone and web-based software from http://cdsfold.trahed.jp/cdsfold/ CONTACTS: terai-goro@aist.go.jp or asai@k.u-tokyo.ac.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Kathrin Leppek; Gun Woo Byeon; Wipapat Kladwang; Hannah K Wayment-Steele; Craig H Kerr; Adele F Xu; Do Soon Kim; Ved V Topkar; Christian Choe; Daphna Rothschild; Gerald C Tiu; Roger Wellington-Oguri; Kotaro Fujii; Eesha Sharma; Andrew M Watkins; John J Nicol; Jonathan Romano; Bojan Tunguz; Fernando Diaz; Hui Cai; Pengbo Guo; Jiewei Wu; Fanyu Meng; Shuai Shi; Eterna Participants; Philip R Dormitzer; Alicia Solórzano; Maria Barna; Rhiju Das Journal: Nat Commun Date: 2022-03-22 Impact factor: 17.694
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