Gap Penalty - Challenges

Challenges

There are a few challenges when it comes to working with gaps. When working with popular algorithms there seems to be little theoretical basis for the form of the gap penalty functions. Consequently, for any alignment situation gap placement must be empirically determined. Also, pairwise alignment gap penalties,such as the affine gap penalty, are often implemented independent of the amino acid types in the inserted or deleted fragment or at the broken ends, despite evidence that specific residue types are preferred in gap regions. Finally, alignment of sequences implies alignment of the corresponding structures, but the relationships between structural features of gaps in proteins and their corresponding sequences are only imperfectly known. Because of this incorporating structural information into gap penalties is difficult to do. Some algorithms use predicted or actual structural information to bias the placement of gaps. However, only a minority of sequences have known structures, and most alignment problems involve sequences of unknown secondary and tertiary structure.