Symmetry-breaking transitions in the early steps of protein self-assembly.

Protein misfolding and subsequent self-association are complex, intertwined processes, resulting in development of a heterogeneous population of aggregates closely related to many chronic pathological conditions including Type 2 Diabetes Mellitus and Alzheimer's disease. To address this issue, here, we develop a theoretical model in the general framework of linear stability analysis. According to this model, self-assemblies of peptides with pronounced conformational flexibility may become, under particular conditions, unstable and spontaneously evolve toward an alternating array of partially ordered and disordered monomers.

Binding of Disordered Peptides to Kelch: Insights from Enhanced Sampling Simulations.

Keap1 protein plays an essential role in regulating cellular oxidative stress response and is a crucial binding hub for multiple proteins, several of which are intrinsically disordered proteins (IDP). Among Kelch's IDP binding partners, NRF2 and PTMA are the two most interesting cases. They share a highly similar binding motif; however, NRF2 binds to Kelch with a binding affinity of approximately 100-fold higher than that of PTMA.

Accelerating the Conformational Sampling of Intrinsically Disordered Proteins.

Intrinsically disordered proteins (IDPs) are a class of proteins lacking a well-defined secondary structure. Instead, they are able to attain multiple conformations, bind to multiple targets, and respond to changes in their surroundings. Functionally, IDPs have been associated with molecular recognition, cell regulation, and signal transduction.

RNA/Peptide Binding Driven by Electrostatics-Insight from Bidirectional Pulling Simulations.

RNA/protein interactions play crucial roles in controlling gene expression. They are becoming important targets for pharmaceutical applications. Due to RNA flexibility and to the strength of electrostatic interactions, standard docking methods are insufficient.

Interactions of iron-sulfur clusters with small peptides: insights into early evolution.

Favoring the stability of iron-sulfur clusters in hydrothermal vents could have been important for the origin of life. It has been postulated that small "nest" peptides with lengths between 3 and 6 residues could have been important to stabilize early iron-sulfur clusters. We present theoretical calculations exploring the sequence and conformational spaces of short peptides able to bind with high affinity the iron-sulfur cluster Fe(4)S(4).

Counterion Redistribution upon Binding of a Tat-Protein Mimic to HIV-1 TAR RNA.

Binding of proteins and small molecules to RNA involves many electrostatic interactions, which may alter the distribution of ions around the RNA molecule. Here, we use molecular dynamics simulations to investigate how binding of a cyclic peptide mimic of the HIV-1 Tat protein affects the ionic distribution around the HIV-1 TAR RNA element. The calculations reproduce the structural properties observed in NMR studies of TAR and its complex.

Bioavailability of metal ions and evolutionary adaptation.

The evolution of life on earth has been a long process that began nearly 3,5 x 109 years ago. In their initial moments, evolution was mainly influenced by anaerobic environments; with the rise of O2 and the corresponding change in bioavailability of metal ions, new mechanisms of survival were created. Here we review the relationships between ancient atmospheric conditions, metal ion bioavailability and adaptation of metals homeostasis during early evolution.