Does Sequence Dictate Structure Which Dictates Function?

Bioinformatics tools and computational methods to predict biomolecular structure from sequence has been and still is in constant development, originally motivated by the Anfinsen’s dogma on protein folding. The dogma was the very basis for the development of the extremely widely accepted notion that “sequence dictates structure which dictates function.” Nonetheless, the dogma does not support the concept of divergent evolution, the most common form of evolution in nature, but support the concept of convergent evolution, creating several major problems in its application to biomolecular structure prediction. Besides, the dogma ignores homology, the most important requirement for the successful use of comparative sequence analysis, which is the most powerful and most widely used Bioinformatics tool to align homologous sequences not only to infer RNA secondary structures accurately, but also derive evolutionary relationships between diverse organisms. Now is the time to revisit the dogma and throw the ingrained and flawed conventional notion away, followed by adopting a new notion: “Function dictates structure which, in turn, dictates sequence.