Optimizing restriction site placement for synthetic genomes

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• 作者：Pablo Montes^a ; ¹ ; ^{pmontes@cs.sunysb.edu} ; Heraldo Memelli^a ; ^{hmemelli@cs.sunysb.edu} ; Charles B. Ward^a ; ² ; ^{charles@cs.sunysb.edu} ; Joondong Kim^b ; ^{jdkim@ams.sunysb.edu} ; Joseph S.B. Mitchell^b ; ^{jsbm@ams.sunysb.edu} ; Steven Skiena^a ; ² ; ^{skiena@cs.sunysb.edu}
• 关键词：Synthetic biology ; Restriction enzyme placement ; Genome refactoring
• 刊名：Information and Computation
• 出版年：2012
• 期刊代码：132_08905401
• 类别：cp
• 出版时间：April, 2012
• 卷：213
• 期：Complete
• 页码：59-69
• 文件大小：705 K

摘要

Restriction enzymes are the workhorses of molecular biology. We introduce a new problem which arises in the course of our project to design virus variants to serve as potential vaccines: we wish to modify virus-length genomes to introduce large numbers of unique restriction enzyme recognition sites while preserving wild-type function by substitution of synonymous codons. We show that the resulting problem is NP-Complete, give an exponential-time algorithm, as well as well-performing heuristics, and give excellent results for five sample viral genomes. Our resulting modified genomes have several times more unique restriction sites and reduce the maximum gap between adjacent sites by three to nine-fold.