5.5 Materials and Methods
6.5.6 Structure Validation
Structures were collected from the RCSB Protein Data Bank [3]. Structure alignments for Figure 6.3 and Figure 6.4 were made using Cn3D [18]. The Cn3D alignments are coloured by identity such that conserved positions are coloured red and non-conserved positions are coloured blue. RMSD for structure alignments was calculated using PyMOL [5]. The struc- ture alignment for Figure 6.5 was created using PyMOL[5]. The entire structure alignment
was rendered using the ‘cartoon’ renderer. Important residues and the NAD cofactor are em- phasized through stick rendering on top of the original alignment. NAD is coloured red. The region of high local covariation is coloured blue.
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Discussion
This work represents a contribution to our collective understanding of sequence alignment, coevolution, and their intertwined relationship. Prior to this work, the alignment-coevolution relationship was not adequately characterized in the literature, which has led to misuses of coevolutionary methods. This work is an attempt to acknowledge the fundamental implicit assumptions made about evolution when conducting sequence analysis experimentsin silico. It is also an advancement of the fields of multiple sequence alignment, and (both directly and indirectly) coevolutionary inference.