Algorithms based on HMMs are able to identify localization motifs by modeling sequence alignments. A test sequence is compared against all the HMM models produced for the various subcellular compartments, and it is assigned to the one with the highest probability score. The success of HMMs is highly dependent upon accurate alignment of the training sequences. Also, HMMs can only cope with linear sequences, and, for this reason, any localization motifs created as a result of the secondary or the tertiary structure cannot be modeled by HMMs. Modeling such 2D or 3D motifs may require alternative probabilistic methodologies such as stochastic context-free grammars (SCFGs). SCFGs have been successfully deployed to assist with the RNA secondary structure prediction  but have found limited application in predicting protein localization.
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