Abstract
The alpha-helical coiled coil can adopt a variety of topologies, among the most common of which are parallel and antiparallel dimers and trimers. We present Multicoil2, an algorithm that predicts both the location and oligomerization state (two versus three helices) of coiled coils in protein sequences. Multicoil2 combines the pairwise correlations of the previous Multicoil method with the flexibility of Hidden Markov Models (HMMs) in a Markov Random Field (MRF). The resulting algorithm integrates sequence features, including pairwise interactions, through multinomial logistic regression to devise an optimized scoring function for distinguishing dimer, trimer and non-coiled-coil oligomerization states; this scoring function is used to produce Markov Random Field potentials that incorporate pairwise correlations localized in sequence. Multicoil2 significantly improves both coiled-coil detection and dimer versus trimer state prediction over the original Multicoil algorithm retrained on a newly-constructed database of coiled-coil sequences. The new database, comprised of 2,105 sequences containing 124,088 residues, includes reliable structural annotations based on experimental data in the literature. Notably, the enhanced performance of Multicoil2 is evident when tested in stringent leave-family-out cross-validation on the new database, reflecting expected performance on challenging new prediction targets that have minimal sequence similarity to known coiled-coil families. The Multicoil2 program and training database are available for download from http://multicoil2.csail.mit.edu.
Highlights
The coiled coil is a protein motif characterized by superhelical twisting of two or more alpha helices around one another
Coiled coils are remarkably prevalent in protein structures, and they adopt a wide range of structural topologies with variations in helix orientation and oligomerization state
The NPS coiled-coil database A new coiled-coil database of 1279 dimers and 333 trimers is derived from three sources: the Paircoil2 training set [9], coiled coils detected in the Protein Data Bank (PDB) using SOCKET, and new coiled-coil families described in the literature
Summary
The coiled coil is a protein motif characterized by superhelical twisting of two or more alpha helices around one another. The repeating sequence motif makes the coiled-coil structure amenable to prediction, and several algorithms have been developed to detect the presence of coiledcoil-forming segments in protein sequence [5]. More complete annotation of structure, requires predicting the number of helices participating in a coiled-coil bundle, as well as the axial alignment and orientation of all helices. Among these aspects of coiled-coil structure, the prediction of oligomerization state has so far received the most attention, work on other aspects of structural specificity is becoming tractable as the number of solved coiled-coil structures grows [6]
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