Conspectus Are all protein interactions fully optimized? Do suboptimal interactions
compromise specificity? What is the functional impact of frustration? Why does evolution not …

NMR spectroscopy is the only method to access the structural dynamics of biomolecules at
high (atomistic) resolution in their native solution state. However, this method's low …

The proposal that coupled folding to binding is not an obligatory mechanism for intrinsically
disordered (ID) proteins was put forward 10 years ago. The notion of fuzziness implies that …

It is becoming increasingly recognised that disordered proteins may be fuzzy, in that they
can exhibit a wide variety of binding modes. In addition to the well-known process of folding …

Dissolution dynamic nuclear polarization (d-DNP) is a versatile method to enhance nuclear
magnetic resonance (NMR) spectroscopy. It boosts signal intensities by four to five orders of …

Many cell signaling pathways are orchestrated by the weak, transient, and reversible protein–
protein interactions that are mediated by the binding of a short peptide segment in one …

Intrinsically disordered proteins (IDPs) carry out many biological functions. They lack a
stable three-dimensional structure, but rather adopt many different conformations in dynamic …

Aggregation of the microtubule-associated protein Tau is a hallmark of Alzheimer's disease
with Tau oligomers suspected as the most toxic agent. Tau is a client of the molecular …

Abstract FuzDB (http://protdyn-database. org) compiles experimentally observed fuzzy
protein complexes, where intrinsic disorder (ID) is maintained upon interacting with a partner …

Highlights•Suboptimal binding motifs lead to frustrated energy landscape.•Non-native,
transient contacts regulate heterogeneity in transition or bound state.•Alternative recognition …