DNA 7 Revised Papers from the 7th International Workshop on DNA-Based Computers: DNA Computing
DNA 7 Revised Papers from the 7th International Workshop on DNA-Based Computers: DNA Computing
The fidelity of dna computation
The fidelity of dna computation
Biologically-implemented genetic algorithm for protein engineering
Proceedings of the 11th Annual conference on Genetic and evolutionary computation
A DNA-Based genetic algorithm implementation for graph coloring problem
ICIC'05 Proceedings of the 2005 international conference on Advances in Intelligent Computing - Volume Part II
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The directed evolution of proteins, using an in vitro domainal shuffling strategy was proposed in (J. Kolkman and W. Stemmer, Nat. Biotech. 19, 423 (2001). Due to backhybridization during parallel overlap assembly, however this method appears unlikely to be an efficient means of iteratively generating massive, combinatorial libraries of shuffled genes. Furthermore, recombination at the domainal level (30-300 residues) appears too coarse to effect the evolution of proteins with substantially new folds. In this work, the compact structural unit, or module (10-25 residues long), and the associated pseudo-module are adopted as the fundamental units of protein structure, so that a protein may be modelled as an N to C-terminal walk on a directed graph composed of pseudomodules. An in vitro method, employing PNA-mediated Whiplash PCR (PWPCR), RNA-protein fusion, and restriction-based recombination is then presented for evolving protein sets with high affinity for a given selection motif, subject to the constraint that each represents a walk on a predefined pseudo-module digraph. Simulations predict PWPCRto be a reasonably high efficiency method of producing massive, recombined gene libraries encoding for proteins shorter than about 600 residues.