Mining tertiary structural motifs for assessment of designability.
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ABSTRACT:
SUBMITTER: Zhang J
PROVIDER: S-EPMC4222026 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
Mining tertiary structural motifs for assessment of designability.
Zhang Jian J Grigoryan Gevorg G
Methods in enzymology 20130101
The observation of a limited secondary-structural alphabet in native proteins, with significant sequence preferences, has profoundly influenced the fields of protein design and structure prediction (Simons, Kooperberg, Huang, & Baker, 1997; Verschueren et al., 2011). In the era of structural genomics, as the size of the structural dataset continues to grow rapidly, it is becoming possible to extend this analysis to tertiary structural motifs and their sequences. For a hypothetical tertiary motif ...[more]
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Project description:The modulation of protein-protein interactions (PPIs) by means of creating or stabilizing secondary structure conformations is a rapidly growing area of research. Recent success in the inhibition of difficult PPIs by secondary structure mimetics also points to potential limitations, because often, specific cases require tertiary structure mimetics. To streamline protein structure-based inhibitor design, we have previously described the examination of protein complexes in the Protein Data Bank where α-helices or β-strands form critical contacts. Here, we examined coiled coils and helix bundles that mediate complex formation to create a platform for the discovery of potential tertiary structure mimetics. Though there has been extensive analysis of coiled coil motifs, the interactions between pre-formed coiled coils and globular proteins have not been systematically analyzed. This article identifies critical features of these helical interfaces with respect to coiled coil and other helical PPIs. We expect the analysis to prove useful for the rational design of modulators of this fundamental class of protein assemblies.
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