AUTOMATED SCREENING OF ENZYME VARIANTS

摘要

Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.

主权项

1. A method, implemented using a computer system that includes one or more processors and system memory, for screening a plurality of different enzyme variants for activity with a substrate, the method comprising:
(a) for each enzyme variant, docking, by the computer system, a computational representation of the substrate to a computational representation of an active site of the enzyme variant, wherein docking (i) generates a plurality of poses of the substrate in the active site, and (ii) identifies energetically favorable poses of the substrate in the active site; (b) for each energetically favorable pose, determining whether the pose is active, wherein an active pose meets one or more constraints for the substrate to undergo catalysis in the active site; and (c) selecting at least one of the enzyme variants determined to have one or more active poses.