Studies On Binding Sites In Intrinsically Disordered Proteins Interacting With Proteins And Nucleic Acids Based On Sequence Features

The traditional structure–function paradigm of proteins considers that function depends ona well defined3D structure. However, in recent years it finds that nearly30%proteins lack stablestructures in their native state but performing key roles in organism, and the proteins are calledintrinsically disordered proteins (IDPs). Their structures are described as highly dynamicensembles of flexible conformations. They play multiple important roles in the cell, such assignal, recognition and regulation. Because of their distinctive structure and function features,intrinsically disordered proteins becoming an important part of modern structural biology andproteomic studies.Intrinsically disordered proteins usually form well-defined structures when binding withother molecules, undergoing disorder-to-order transitions which are crucial for their functions.However, there are few studies on the prediction of binding sites between IDPs and proteins ornucleic acids because the related data and resource pinch, and the existing prediction methods donot consider the differences of sequence features between disorder and order regions. Therefore,we studies the binding sites in intrinsically disordered proteins interacting with proteins andnuclei acids from sequence features, and analyze the applicability of the current leading methodspredicting binding sites of proteins in IDPs.First, the databases of IDPs-DNA、IDPs-RNA and IDPs-proteins are set up based on DisProtand PDB and all the binding sites are found out. Based on the databases, the subsets areconstructed on the disorder and the order regions. The results indicate that, there are morebinding sites in the disordered regions than in the order regions whether the interactingmolecules are proteins or nuclei acids. Then we discuss theK2of all binding sites in alldatabases, which showsK2in the binding sites is smaller than in the total amino acid sequencesand its distributed range is wider, which show that there is smaller difference of the compositionfrequency of amino acids in the binding site regions and there are bigger difference in thedisordered regions. Third, we study the binding properties of binding sites and binding pairs. The results tell us that the binding sites prefer to polar amino acids and the binding pairs commonlyoccur between e and G. So the charge, dipole scale and volume scale of the amino acids haveimportant impact effect in the interaction process. The binding properties in the disordered andthe ordered regions are similar to most amino acids. At last, we predict the binding sites in theintrinsically disordered proteins interacting with DNA and RNA using the current predictingmethods on binding sites of protein-DNA and RNA. From the prediction results, we can find outthe differences of the sequence features between the disordered and the ordered regions. So theeffect of disorder and order should be considered when develop new predicting method onbinding sites of IDPs-DNA and RNA. In brief, this work can provide data support aboutdeveloping novel predicting binding sites in intrinsically disordered proteins interacting withDNA and RNA.