タンパク質立体構造情報を利用した機能予測法fcanal：酵素・結合タンパク質への応用

Abstract

Structural genomics projects are beginning to produce protein structures with unknown functions, therefore, high-throughput methods for predicting functions are necessary. Although sequence based function prediction methods have been applied extensively, structure based prediction is believed to provide higher specificity and sensitivity because functions are closely related to three-dimensional structures of functional sites which are more strongly conserved during evolution than sequence.We have developed FCANAL, a method to predict functions using the score matrix obtained from the distances between C α atoms and frequencies of appearance [1]. The previous report used key residues predicted from sequence comparison (motifs). In this report, we expanded the method to enzymes and binding proteins with key residues predicted on the basis of three-dimensional structures. Using FCANAL, we constructed score matrices for 31 enzymes. When we applied them to all the structure entries deposited at the Protein Data Bank, FCANAL could detect functional sites with high accuracy. This suggests that the FCANAL will help identify the functions of newly determined structures and pinpoint their functionally important regions.

The FEATURE framework for protein function annotation: modeling new functions, improving performance, and extending to novel applications

“…Annotation of molecular function by similarity is possible on the structural level as on the sequence level – by evaluating the similarity of global folds or local environments [ 7 ]. Structural similarity methods may employ chemical, physical, energetic or geometric criteria to recognize functional environments [ 8 - 10 ].…”

“…Given its ubiquity, it comes as no surprise that there are numerous tools for recognizing function based on sequence. Pfam, Panther [ 32 ], PROSITE, and Superfamily [ 33 ] are just a few of the publicly available databases and methods for characterizing protein families or functions; many of them are conglomerated into single integrated tools like InterProScan [ 34 ] and ProFunc [ 8 , 10 ].…”