Evolution versus Design: Template-Directed Self-Assembly of Peptides to Artificial Proteins (TASP)

Abstract

Protein design and mimicry combines elements of synthetic organic chemistry with structural and functional aspects of biological relevance in a unique way. Due to progress in this interdisciplinary research field, access to molecules featuring some essential properties of native proteins appears to be within reach, enabling the complex mechanisms in molecular recognition processes to be deciphered. Since its introduction by the authors, the template approach in protein de novo design (Template Assembled Synthetic Proteins, TASP) has experienced a broad conceptual diversification. Starting from today's state-of-the-art in protein design, we present here some ongoing work in the Lausanne laboratories focusing on the use of regioselectively addressable templates and TASP scaffolds for addressing fundamental questions in peptide assembly, protein folding and mimicry. It is shown that the developed concepts can ideally reconcile evolutionary and rational design principles for creating molecules of biological and therapeutic interest.