Identifying Intrinsic Disorder by Sequence Homology

Abstract

Amino acid sequence determines 3D protein structure [1], with (Amino Acid Sequence) → (3D Structure) → (Function) currently being the main paradigm for the analysis of genomic protein sequences. However, there are many proteins that perform their functions and yet do not fold into specific 3D structure. The existence of such “intrinsic disorder” has led to a call for a re-assessment of the protein structure/function paradigm [4]. The focus of our work over the last few years has been the identification, analysis and prediction of intrinsic disorder [2, 3]. A major limitation of this work has been the dearth of intrinsically disordered protein examples. Here we report use of homology-based methods to find intrinsically disordered protein segments. The result is a collection currently containing 42 protein families that have 691 sequences in total, with 65,821 putative intrinsically disordered amino acids.