Minimal-alphabet proteins by evolution, engineering, and design.

Filip Buchel¹, Valerio G Giacobelli², Klára Hlouchová³

¹Department of Cell Biology, Charles University, 12843 Prague, Czech Republic; Department of Biochemistry, Charles University, 12843 Prague, Czech Republic.

²Department of Cell Biology, Charles University, 12843 Prague, Czech Republic; Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16000 Prague, Czech Republic.

³Department of Cell Biology, Charles University, 12843 Prague, Czech Republic; Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16000 Prague, Czech Republic. Electronic address: klara.hlouchova@natur.cuni.cz.

PubMed DOI

Abstract

Research on the structural and functional potential of minimal amino acid alphabets is shifting from reductive 'pruning' of extant proteins to bottom-up exploration of combinatorial sequence space. This review highlights the experimental and computational toolkits driving this transition. We discuss how solid-phase peptide synthesis, genetically encoded libraries, and high-throughput selection and…

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