講演者の古賀さんは天然に存在しないアミノ酸配列と立体構造を持つタンパク質の合理設計と実証に世界で初めて成功しました。本セミナーでは、合理設計でタンパク質を創る技術の最前線についてご紹介して頂きます。

Protein molecules fold into unique tertiary structures specified by their amino acid sequences from random coils, and then exert functions based on the folded structures. Many naturally occurring protein structures have been determined for understanding principles for folding and functions. However, long evolutional histories of naturally occurring proteins prevent us to uncover the principles. Designing protein molecules from scratch provides us opportunities to explore the principles: hypothesis on folding and functions can be evaluated by computationally designing proteins and experimentally assessing how they behave. We carried out a study of designing ideal protein structures, which are completely optimized for folding, to investigate how they fold into unique tertiary structures. We discovered a set of rules relating secondary structure patterns to protein tertiary motifs, which make possible the design of strongly funneled protein folding energy landscapes. Guided by these rules, we computationally designed sequences predicted to fold into ideal protein structures consisting of alpha helices, beta strands, and minimal loops.
 Designs for various topologies were found to be monomeric, very stable, and adopt structures in solution nearly identical to the computational models.
 These results illuminate how proteins fold into unique tertiary structures.