Heligeom: A web resource to generate, analyze, and visualize filament architectures based on pairwise association geometries of biological macromolecules.

Abstract

At the subcellular level, macromolecules self-assemble to form molecular machinery in which the assembly modes play critical roles: the structural integrity of cell walls that allows mechanical growth, the maintenance and repair of the genetic material, membrane flow control, protein chaperoning, and ATP production, to cite just a few examples. As molecular modeling expands its scope to such systems, structural biologists are faced with the difficulty of understanding the structure and dynamics of these supramolecular assemblies. We present Heligeom, a webserver that offers a simple and efficient means for analyzing and constructing oligomeric assemblies based on user-provided structures of two interacting units. The input 3D coordinates may result from structure determination, simulations, docking trials, or deep-learning tools such as AlphaFold. For a given interface, Heligeom outputs the mathematical helical parameters of the corresponding oligomeric form, including axis, pitch, handedness, number of monomers per turn, etc. The server also allows leveraging these parameters to construct oligomers of specified size, visualizing them interactively, and downloading them as PDB files. For subunits (protomers) having multiple interaction geometries, the different interfaces and their global assembly geometry can be visualized and compared. Heligeom thus allows explicitly linking protomer-protomer interfaces to the oligomeric architecture, illuminating possible sources of plasticity in protein filaments such as mutations or thermal, mechanical, or chemical perturbations. Heligeom thus constitutes an intuitive tool to accompany integrative modeling of oligomeric filamentous assemblies. Examples of its application at different structural levels are presented. Heligeom webserver can be accessed at https://heligeom.galaxy.ibpc.fr.