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A large amount of proteomic data is being generated due to the advancements in high-throughput genome sequencing. But the rate of functional annotation of these sequences falls far behind. To fill the gap between the number of sequences and their annotations, fast and accurate automated annotation methods are required. Many methods, such as GOblet, GOfigure, and Gotcha, are designed based on the BLAST search. Unfortunately, the sequence coverage of these methods is low as they cannot detect the remote homologues. The lack of annotation coverage of the existing methods advocates novel methods to improve protein function prediction. Here we present a automated protein functional assignment method based on the neural response algorithm, which simulates the neuronal behavior of the visual cortex in the human brain. The main idea of this algorithm is to define a distance metric that corresponds to the similarity of the subsequences and reflects how the human brain can distinguish different sequences. Given query protein, we predict the most similar target protein using a two layered neural response algorithm and thereby assigned the GO term of the target protein to the query. Our method predicted and ranked the actual leaf GO term among the top 5 probable GO terms with 87.66% accuracy. Results of the 5-fold cross validation and the comparison with PFP and FFPred servers indicate the prominent performance by our method. The NRProF program, the dataset, and help files are available at http://www.jjwanglab.org/NRProF/.