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The biologic motivation of our study is to recognize common structure patterns in \"immunoevasins\", proteins mediating virus evasion of host immune defense. Our experimental study, using both viral and non-viral proteins, demonstrates the efficiency and efficacy of the proposed method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We present a theoretic framework, offer a practical software implementation for incorporating prior domain knowledge, such as substitution matrices as studied here, and devise an efficient algorithm to identify approximate matched frequent subgraphs. By doing so, we significantly expanded the analytical power of sophisticated data mining algorithms in dealing with large volume of complicated and noisy protein structure data. 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