Many proposed statistical measures can efficiently compare protein sequence to further infer protein structure, function and evolutionary information. They share the same idea of using k-word frequencies of protein sequences. Given a protein sequence, the information on its related protein sequences hasnt been used for protein sequence comparison until now. This paper proposed a scheme to construct protein sequence space which was associated with protein sequences related to the given protein, and the performances of statistical measures were compared when they explored the information on protein sequence space or not. This paper also presented two statistical measures for protein: gre.k (generalized relative entropy) and gsm.k (gapped similarity measure).