CCCP

CCCP implements the Crick parameterization to parameterize coiled-coil and other helical protein structures and to delineate the designable structural space relevant to de novo protein design.

Key Features:

• Crick parameterization: Applies the Crick parameterization to coiled-coil structures and shows that over 95% of known α-helical coiled-coil structures fall within a 1-Å C(α) root mean square deviation (RMSD) from an idealized Crick backbone.
• Restricted geometric space: Reveals a highly constrained set of "allowed" coiled-coil conformations characterized by restricted axial offsets between helices with differences between parallel and anti-parallel configurations; preferred superhelical radii that correlate linearly with oligomerization state; amino acid propensities at α- and d-positions that depend on radius; and discrete rotational angles of helices about their axes that are consistent regardless of oligomerization state or orientation.
• Design space reduction: Estimates a reduction in the space of designable coiled-coil structures by at least 160-fold compared to geometrically feasible structures.
• Generalized helical parameterization framework: Provides a general mathematical framework for parameterizing arbitrary helical structures that reduces to the Crick parameterization as a special case and has been validated on non-coiled-coil helical bundles found in channels and transporter proteins.
• Parameter fitting and structure generation: Includes computational routines for coiled-coil parameter fitting and for generating structures from fitted parameters.

Scientific Applications:

• De novo protein design: Narrows candidate coiled-coil architectures and quantifies structural constraints to guide sequence-based design of novel coiled-coil assemblies.
• Structural biology research: Enables analysis of geometric and functional diversity of α-helical coiled coils and other helical bundles to inform studies of folding and stability.
• Biotechnological applications: Provides structural parameter insights that can be applied to engineering proteins with specific geometric and interaction properties for industrial or therapeutic purposes.

Methodology:

Computational methods explicitly include application of the Crick parameterization to coiled coils, coiled-coil parameter fitting, structure generation from parameters, and a generalized mathematical helical parameterization validated on non-coiled-coil helical bundles in channels and transporter proteins.