Assembly of Biomolecular Gigastructures and Visualization with the Vulkan Graphics API.

Kornel Ozvoldik,Burkhard Rammner,Elmar Krieger,Thomas Stockner

doi:10.1021/acs.jcim.1c00743

Kornel Ozvoldik, Burkhard Rammner + Show 2 more

Open Access

https://doi.org/10.1021/acs.jcim.1c00743

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Abstract

Building and displaying all-atom models of biomolecular structures with millions or billions of atoms, like virus particles or cells, remain a challenge due to the sheer size of the data, the required levels of automated building, and the visualization limits of today’s graphics hardware. Based on concepts introduced with the CellPack program, we report new algorithms to create such large-scale models using an intermediate coarse-grained “pet representation” of biomolecules with 1/10th the normal size. Pet atoms are placed such that they optimally trace the surface of the original molecule with just ∼1/50th the original atom number and are joined with covalent bonds. Molecular dynamics simulations of pet molecules allow for efficient packing optimization, as well as the generation of realistic DNA/RNA conformations. This pet world can be expanded back to the all-atom representation to be explored and visualized with full details. Essential for the efficient interactive visualization of gigastructures is the use of multiple levels of detail (LODs), where distant molecules are drawn with a heavily reduced polygon count. We present a grid-based algorithm to create such LODs for all common molecular graphics styles (including ball-and-sticks, ribbons, and cartoons) that do not require monochrome molecules to hide LOD transitions. As a practical application, we built all-atom models of SARS-CoV-2, HIV, and an entire presynaptic bouton with 1 μm diameter and 3.6 billion atoms, using modular building blocks to significantly reduce GPU memory requirements through instancing. We employ the Vulkan graphics API to maximize performance on consumer grade hardware and describe how to use the mmCIF format to efficiently store such giant models. An implementation is available as part of the YASARA molecular modeling and simulation program from www.YASARA.org. The free YASARA View program can be used to explore the presented models, which can be downloaded from www.YASARA.org/petworld, a Creative Commons platform for sharing giant biomolecular structures.

Highlights

Experimental structure determination depends on the availability of large numbers of structurally identical copies that can be averaged, either in an X-ray crystal, in an NMR solution, or on a cryo-EM layer
Two published approaches to mesoscale modeling are CellPack, which uses cooking recipes in XML or JSON format to describe how a model can be built automatically from its ingredients,[4] and Marion, which takes an interactive approach and uses a graphical user interface to build a model with a set of rules.[5,6]
We describe a new functionality added to the YASARA molecular modeling and simulation program[7−9] to construct mesoscale models from modular building blocks and visualize them using all common molecular graphics styles

Summary

■ INTRODUCTION

Experimental structure determination depends on the availability of large numbers of structurally identical copies that can be averaged, either in an X-ray crystal, in an NMR solution, or on a cryo-EM layer. Molecules are scaled to 1/10th the normal size and represented by pet atoms, which require only 2% of the original atom number. This allows for efficient collision detection to generate tight packings as well as large-scale coarse-grained molecular dynamics (MD) simulations, for example, to insert the HIV RNA into its capsid core. An infrastructure for sharing these macros and the generated mesoscale models has been set up at www.YASARA.org/ petworld

■ RESULTS AND DISCUSSION

■ MATERIALS AND METHODS

■ ACKNOWLEDGMENTS

■ REFERENCES