Specificity and characteristics of fuzzy complexes -- Modelling of intrinsically disordered proteins

Abstract: Intrinsically disordered proteins are fully functional proteins without a three-dimensional structure. Intrinsically disordered proteins can, in the same way as ordered proteins, interact with other proteins to fulful their function. When intrinsically disordered proteins interact with other proteins they can form complexes, so-called fuzzy complexes, with different degrees of disorder still present. Fuzzy complexes are found in a number of different places, e.g. in transcription factors. This thesis will try to answer the question, if and how specificity is affected by fuzziness, and how different characteristics affect fuzziness. This is done by a coarse-grained model with two protein chains, the target and the probe. The first step is a design process where the probe learns the target. The second step is a recognition step, where the probe is exposed to a number of different rival targets and will have to recognise the original target. The last step investigates the characteristics of the target. The design process is repeated for targets with different characteristics. The model uses ordered and fuzzy complexes that are modeled in two different cases, with only hydrophobic - polar (HP) amino acids and all with twenty amino acids (20x20), respectively. It was found that fuzzy complexes can interact in a specific way, but they are less specific than ordered complexes. This means that fuzzy complexes can interact specifically with a number of different proteins. No clear trend was found between the characteristics of the target and the fuzziness of the probe.