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A novel pattern recognition algorithm called an orthogonal kernel machine (OKM) is presented for the prediction of functional sites in proteins. Two novelties in OKM are that the kernel function is specially designed for measuring the similarity between a pair of protein sequences and the kernels are selected using the orthogonal method. Based on a set of well-recognized orthogonal kernels, this algorithm demonstrates its superior performance compared with other methods. An application of this algorithm to a real problem is presented.