Predicting Protein Function Using Homology-Based Methods

Abstract

The molecular function of a protein can be deduced by analysing the ‘homology’ that exists due to common evolutionary ancestry among different organisms, while the cellular function can be inferred by focussing on the interactions between specific proteins. The molecular function could be predicted based on methods that rely on comparing a sequence to another sequence of known function as proteins having similar sequences are usually homologous performing similar function. On the other hand, in order to detect remote homologs or sequences which are very divergent, sequence-profile comparison methods were developed which use profile hidden Markov model (HMM). A profile HMM is generated from an alignment of multiple sequences and inherits more information than a single sequence. More advanced methods use profile-profile comparison methods to detect homology among sequences having very low sequence identity. In general, given a protein sequence with unknown function, these methods are used in a hierarchical manner to identify the function and serve as powerful annotation tools for predicting the function of a novel protein. With many genomes currently being sequenced, knowledge of these methods for annotation is increasingly becoming important.