A High-Throughput Workflow to Analyze Sequence-Conformation Relationships and Explore Hydrophobic Patterning in Disordered Peptoids.

Understanding how a macromolecule's primary sequence governs its conformational landscape is crucial for elucidating its function, yet these design principles are still emerging for macromolecules with intrinsic disorder. Herein, we introduce a high-throughput workflow that implements a practical colorimetric conformational assay, introduces a semi-automated sequencing protocol using MALDI-MS/MS, and develops a generalizable sequence-structure algorithm. Using a model system of 20mer peptidomimetics containing polar glycine and hydrophobic -butylglycine residues, we identified nine classifications of conformational disorder and isolated 122 unique sequences across varied compositions and conformations.

Competition between β-Sheet and Coacervate Domains Yields Diverse Morphologies in Mixtures of Oppositely Charged Homochiral Polypeptides.

Biomolecular assembly processes involving competition between specific intermolecular interactions and thermodynamic phase instability have been implicated in a number of pathological states and technological applications of biomaterials. As a model for such processes, aqueous mixtures of oppositely charged homochiral polypeptides such as poly-l-lysine and poly-l-glutamic acid have been reported to form either β-sheet-rich solid-like precipitates or liquid-like coacervate droplets depending on competing hydrogen bonding interactions. Herein, we report studies of polypeptide mixtures that reveal unexpectedly diverse morphologies ranging from partially coalescing and aggregated droplets to bulk precipitates, as well as a previously unreported re-entrant liquid-liquid phase separation at high polypeptide concentration and ionic strength.

Molecular Context of Dopa Influences Adhesion of Mussel-Inspired Peptides.

Improving adhesives for wet surfaces is an ongoing challenge. While the adhesive proteins of marine mussels have inspired many synthetic wet adhesives, the mechanisms of mussel adhesion are still not fully understood. Using surface forces apparatus (SFA) measurements and replica-exchange and umbrella-sampling molecular dynamics simulations, we probed the relationships between the sequence, structure, and adhesion of mussel-inspired peptides.

Significant Performance Enhancement of Polymer Resins by Bioinspired Dynamic Bonding.

Marine mussels use catechol-rich interfacial mussel foot proteins (mfps) as primers that attach to mineral surfaces via hydrogen, metal coordination, electrostatic, ionic, or hydrophobic bonds, creating a secondary surface that promotes bonding to the bulk mfps. Inspired by this biological adhesive primer, it is shown that a ≈1 nm thick catecholic single-molecule priming layer increases the adhesion strength of crosslinked polymethacrylate resin on mineral surfaces by up to an order of magnitude when compared with conventional primers such as noncatecholic silane- and phosphate-based grafts. Molecular dynamics simulations confirm that catechol groups anchor to a variety of mineral surfaces and shed light on the binding mode of each molecule.

Molecularly Smooth Self-Assembled Monolayer for High-Mobility Organic Field-Effect Transistors.

Despite the need for molecularly smooth self-assembled monolayers (SAMs) on silicon dioxide surfaces (the most common dielectric surface), current techniques are limited to nonideal silane grafting. Here, we show unique bioinspired zwitterionic molecules forming a molecularly smooth and uniformly thin SAM in "water" in <1 min on various dielectric surfaces, which enables a dip-coating process that is essential for organic electronics to become reality. This monomolecular layer leads to high mobility of organic field-effect transistors (OFETs) based on various organic semiconductors and source/drain electrodes.

Assessing protein conformational sampling and structural stability via de novo design and molecular dynamics simulations.

Molecular dynamics and de novo techniques, associated to quality parameter sets, have excelled at determining the structure of small proteins with high accuracy. To achieve a detailed description of protein conformations, these methods must critically assess the thermodynamic features of the molecular ensembles. Here, a comparison of the conformational ensemble generated by molecular dynamics and de novo techniques were carried out for six Top7-based proteins carrying gp41 HIV-1 epitopes.