A novel method for predicting the secondary structures of proteins from amino acid sequence has been presented. The protein secondary structure seqlets that are analogous to the words in natural language have been extracted. These seqlets will capture the relationship be-tween amino acid sequence and the secondary structures of proteins and further form the protein secondary structure dictionary. To be elaborate, the dictionary is organism-specific. Protein sec-ondary structure prediction is formulated as an integrated word segmentation and part of speech tagging problem. The word-lattice is used to represent the results of the word segmentation and the maximum entropy model is used to calculate the probability of a seqlet tagged as a certain secondary structure type. The method is markovian in the seqlets, permitting efficient exact cal-culation of the posterior probability distribution over all possible word segmentations and their tags by viterbi algorithm. The optimal segmentations and their tags are computed as the results of protein secondary structure prediction. The method is applied to predict the secondary struc-tures of proteins of four organisms respectively and compared with the PHD method. The results show that the performance of this method is higher than that of PHD by about 3.9% Q3 accuracy and 4.6% SOV accuracy. Combining with the local similarity protein sequences that are obtained by BLAST can give better prediction. The method is also tested on the 50 CASP5 target proteins with Q3 accuracy 78.9% and SOV accuracy 77.1%. A web server for protein secondary structure prediction has been constructed which is available at http://www.insun.hit.edu.cn:81/demos/bi-ology/index.html.
