What Would an Alien Amino Acid Alphabet Look Like and Why?

Life on Earth builds genetically encoded proteins by using a standard alphabet of just 20 L-α-amino acids, although many others were available to life's origins and early evolution. To better understand the causes of this foundational evolutionary outcome, we extend previous analyses which have identified a highly unusual distribution of biophysical properties within the set used by life. Specifically, we use a heuristic search algorithm to identify other sets of amino acids, from a library of plausible alternatives, that emulate life's signature.

CoLiDe: Combinatorial Library Design tool for probing protein sequence space.

Motivation: Current techniques of protein engineering focus mostly on re-designing small targeted regions or defined structural scaffolds rather than constructing combinatorial libraries of versatile compositions and lengths. This is a missed opportunity because combinatorial libraries are emerging as a vital source of novel functional proteins and are of interest in diverse research areas.

Results: Here, we present a computational tool for Combinatorial Library Design (CoLiDe) offering precise control over protein sequence composition, length and diversity.