When Data Are Lacking: Physics-Based Inverse Design of Biopolymers Interacting with Complex, Fluid Phases.

Biomolecular research traditionally revolves around comprehending the mechanisms through which peptides or proteins facilitate specific functions, often driven by their relevance to clinical ailments. This conventional approach assumes that unraveling mechanisms is a prerequisite for wielding control over functionality, which stands as the ultimate research goal. However, an alternative perspective emerges from physics-based inverse design, shifting the focus from mechanisms to the direct acquisition of functional control strategies.

CGCompiler: Automated Coarse-Grained Molecule Parametrization via Noise-Resistant Mixed-Variable Optimization.

Coarse-grained force fields (CG FFs) such as the Martini model entail a predefined, fixed set of Lennard-Jones parameters (building blocks) to model virtually all possible nonbonded interactions between chemically relevant molecules. Owing to its universality and transferability, the building-block coarse-grained approach has gained tremendous popularity over the past decade. The parametrization of molecules can be highly complex and often involves the selection and fine-tuning of a large number of parameters (e.

TatA and TatB generate a hydrophobic mismatch important for the function and assembly of the Tat translocon in Escherichia coli.

The twin-arginine translocation (Tat) system serves to translocate folded proteins across energy-transducing membranes in bacteria, archaea, plastids, and some mitochondria. In Escherichia coli, TatA, TatB, and TatC constitute functional translocons. TatA and TatB both possess an N-terminal transmembrane helix (TMH) followed by an amphipathic helix.

Quantifying Membrane Curvature Sensing of Peripheral Proteins by Simulated Buckling and Umbrella Sampling.

Membrane curvature plays an essential role in the organization and trafficking of membrane associated proteins. Comparison or prediction of the experimentally resolved protein concentrations adopted at different membrane curvatures requires direct quantification of the relative partitioning free energy. Here, we present a highly efficient and simple to implement a free-energy calculation method which is able to directly resolve the relative partitioning free energy of proteins as a direct function of membrane curvature, i.

Membrane Thinning Induces Sorting of Lipids and the Amphipathic Lipid Packing Sensor (ALPS) Protein Motif.

Heterogeneities (e.g., membrane proteins and lipid domains) and deformations (e.