Projects per year
Directed evolution emulates the process of natural selection to produce proteins with improved or altered functions. These approaches have proven to be very powerful but are technically challenging and particularly time and resource intensive. To bypass these limitations, we constructed a system to perform the entire process of directed evolution in silico. We employed iterative computational cycles of mutation and evaluation to predict mutations that confer high-affinity binding activities for DNA and RNA to an initial de novo designed protein with no inherent function. Beneficial mutations revealed modes of nucleic acid recognition not previously observed in natural proteins, highlighting the ability of computational directed evolution to access new molecular functions. Furthermore, the process by which new functions were obtained closely resembles natural evolution and can provide insights into the contributions of mutation rate, population size and selective pressure on functionalization of macromolecules in nature. [Figure not available: see fulltext.].
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1/01/19 → 9/10/20