Structure comparison is used to reveal the similarity between protein structures. Every method has its own strength and weakness and the assessment parameters need to be appropriate to the original question on performance of the method. Here, we have assessed three multiple structure-based sequence alignment programs and compared their results. The results suggest that superfamily members which have low sequence identity (<40%) can be aligned using flexible structure alignment methods followed by methods which consider multiple structural features like COMPARER. This kind of structural analysis protocol appears to produce more relevant results, due to consideration of large number of structural features, rather than pure geometric features.