Biology subjects

Fries, C. N.

Publications and source records attributed to Fries, C. N..

3 recordsLinked to original sources

bioRxiv2026

Discovering and designing multistate protein assemblies

Evolved protein assemblies exploit multiple weak interfaces to package cargo, facilitate metabolism, and direct cell movement, often through architectures that depart from strict geometric symmetry. Designed protein assemblies can also break symmetry through conformational flexibility or strain-based defects, but have generally lacked the capacity for large-scale structural rearrangements characteristic of evolved systems. Here, we characterize the structures and biophysical properties of emergent protein assemblies and establish a strategy for designing quasisymmetric materials that switch between assembly states. Rather than relying on intrinsic flexibility, our approach programs multiple self-assembling interfaces onto rigid oligomers. Using multistate design and ensemble predictions, we generate assemblies in which protomers can adopt alternative designed interface modes, enabling identical amino acid sequences to form distinct configurations depending on assembly pathway and environmental conditions. As a proof of principle, we construct quasisymmetric capsids that transition into micron-scale 2D arrays in response to temperature. This work establishes a strategy for encoding alternative assembly geometries within a single protein sequence and provides a foundation for engineering materials with environmentally tunable properties.

biochemistry↗

bioRxiv2026

Designed nanofiber immunogens prime antibody responsesto diverse conformations of the HIV-1 fusion peptide

Focusing antibody responses towards known neutralizing epitopes is a major strategy for protective immunization. Targeting flexible antigenic regions represents a unique challenge because functional antibodies must be able to bind the epitope of interest in multiple conformations. The fusion peptide (FP) of HIV-1 is a flexible peptide critical to viral entry of host cells for which broadly neutralizing antibodies have been identified. Because elicitation of potent, functional antibodies toward this epitope remains an unmet challenge in HIV-1 vaccination, we introduce a designed immunogen platform capable of raising anti-FP-antibodies with increased conformational tolerance relative to a traditional carrier protein. Antibodies induced by these immunogens bind heterologous FP sequences when elicited in mice and infant non-human primates. This platform shows promise for preclinical development to prime antibody responses toward FP of the HIV-1 envelope and can likely be translated to peptide immunofocusing for other viral pathogens.

bioengineering↗

bioRxiv2022

Fast and versatile sequence-independent protein docking for nanomaterials design using RPXDock

Computationally designed multi-subunit assemblies have shown considerable promise for a variety of applications, including a new generation of potent vaccines. One of the major routes to such materials is rigid body sequence-independent docking of cyclic oligomers into architectures with point group or lattice symmetries. Current methods for docking and designing such assemblies are tailored to specific classes of symmetry and are difficult to modify for novel applications. Here we describe RPXDock, a fast, flexible, and modular software package for sequence-independent rigid-body protein docking across a wide range of symmetric architectures that is easily customizable for further development. RPXDock uses an efficient hierarchical search and a residue-pair transform (RPX) scoring method to rapidly search through multidimensional docking space. We describe the structure of the software, provide practical guidelines for its use, and describe the available functionalities including a variety of score functions and filtering tools that can be used to guide and refine docking results towards desired configurations. Author SummaryProtein design methodologies are now able to generate, through a stepwise approach, a wide variety of self-assembling protein structures that begin to rival the structural complexity of naturally occurring protein nanomachines. Efficient methods for docking oligomeric protein building blocks in user-defined target symmetries are central to these techniques. We developed RPXDock as a fast and versatile method to systematically dock pre-existing proteins together into a multitude of asymmetrical and symmetrical architectures. RPXdock is also readily extendable to future applications through the addition of new symmetries, score functions, and filtering criteria.

bioengineering↗