Sequence divergence of orthologous proteins enables adaptation to a plethora of
environmental stresses and promotes evolution of novel functions. As one of the most …

Sequence divergence of orthologous proteins enables adaptation to environmental stresses
and promotes evolution of novel functions. Limits on evolution imposed by constraints on …

Over the past decades, the TIM‐barrel fold has served as a model system for the exploration
of how changes in protein sequences affect their structural, stability, and functional …

Highlights•In-depth sequence analysis reveals that the protein fold universe is more
evolutionarily connected than previously assumed.•Short ancestral fragments are observed …

After the surprisingly low number of genes identified in the human genome, alternative
splicing emerged as a major mechanism to generate protein diversity in higher eukaryotes …

The ability to finely control the structure of protein folds is an important prerequisite to
functional protein design. The TIM barrel fold is an important target for these efforts as it is …

De novo protein design expands the protein universe by creating new sequences to
accomplish tailor‐made enzymes in the future. A promising topology to implement diverse …

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the
TIM-barrel fold. Here we describe the computational design of four-fold symmetrical (β/α) 8 …

The TIM barrel is one of the oldest and most ubiquitous protein folds and is often referred to
as the most successful in nature, due to its capability to host a diverse set of functions. This …

The ability to finely control the structure of protein folds is an important prerequisite to
functional protein design. The TIM barrel fold is an important target for these efforts as it is …