The design of idealized α/β-barrels: Analysis of β-sheet closure requirements

✍ Scribed by Ignace Lasters; Shoshana J. Wodak; Fredric Pio

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 773 KB
• Volume: 7
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/prot.340070306

✦ Synopsis

Abstract

The 8‐old parallel α/β‐barrel topology is encountered in proteins that display an impressive variety of functions, suggesting that this topology may be a rather nonspecific and stable folding motif. Consequently, this motif can be considered as an interesting framework to design novel proteins. It has been shown that the shape of the β‐sheet portion of the barrel can be approximated by a hyperboloid. This geometric object may therefore be used as a scaffold to construct an idealized eight‐standard β‐barrel. To facilitate the de novo design of such structures, a collection of modelling tools has been developed allowing secondary structure elements to be mapped onto the scaffold surface and rotation and translation operations to be performed about user defined axes while evaluating their contribution to the conformational energy of the system. These tools have been applied in a systematic study assessing the ϕ, ψ requirements to design symmetric eight standard β barrels with optimal hydrogen bonding between adjacent β‐strands. It is observed that: (a) the β‐sheet structure can be closed without introducing irregular stagger between β‐strands and (b) the region of ϕ, ψ dihedral angle space compatible with the formation of regular symmetric eight standard β‐barrels coincides with the ϕ, ψ region corresponding to average β‐strands in known protein structures, suggesting that barrel closure does not impose gross constraints on β‐strand geometry.