The concept of quinary interactions as an organizing principle in cells is receiving renewed attention as researchers in the physical and chemical sciences begin to tackle increasingly molecular aspects of biological complexity. This workshop will explore and discuss the continuum of complexity as the molecular sciences moves from studying single proteins and molecular machines in dilute, in vitro systems, to crowded in vitro systems, to cells. Discussion of experimental, theoretical, and computational approaches at each scale will be mixed with discussion of applications where, ideally, a single system of biological interest has been studied at different scales of complexity using a multiplicity of methods. We aim to identify and promote the intensive discussion of current challenges in this field, with the goal to brainstorm about innovative new methods to measure and model quinary interactions with molecular resolution in realistic environments.

More specifically, we intend to discuss three general conceptual themes, which will be discussed with concrete biological examples including ribosomal stalling dynamics, capturing weak protein interactions, and phase separation in cells:

- Machinery in the cell covers a size range from more dissipative to more mechanical systems. Entropy-enthalpy compensation often defines the properties of such machinery, producing low free energy barriers that make the machinery operable while still rising above background noise. Paradigms from mechanical levers to diffusion-controlled networks, and everything in-between can be used to describe this machinery.

- While engineers generally assemble machinery permanently, the cell often has more transient solutions. Quinary structure binds proteins or RNAs transiently and weakly for functional purposes, whereas quaternary structure is more robust. Liquid phase separation compartmentalizes molecules without membrane boundaries, but one has to wonder why not everything phase-separates in as complex a mixture as the cytoplasm. Spliceosomes undergo extensive assembly and disassembly every time they are needed, being more of a "toolkit" than a solid machine like the ribosome. How does Nature utilize the full spectrum from strongly to weakly assembled components?

- Cell fitness is foremost about survival, not efficiency. While many cellular processes operate close to the thermodynamic limit and are thus "efficient," others are accidents of evolution, or they appear unnecessarily complex on the surface until one asks how cells become so robust. In human-engineered systems, robustness is usually a consequence of making each part highly resilient, but removal of a single part causes malfunction; in cellular systems, most parts can be removed without causing the overall machinery to collapse, even though the occasional part, like a very strong protein-protein interaction, is also highly resilient.