OpenABC enables flexible, simplified, and efficient GPU accelerated simulations of biomolecular condensates

Abstract

Biomolecular condensates are important structures in various cellular processes but are challenging to study using traditional experimental techniques. In silico simulations with residue-level coarse-grained models strike a balance between computational efficiency and chemical accuracy. They could offer valuable insights by connecting the emergent properties of these complex systems with molecular sequences. However, existing coarse-grained models often lack easy-to-follow tutorials and are implemented in software that is not optimal for condensate simulations. To address these issues, we introduce OpenABC, a software package that greatly simplifies the setup and execution of coarse-grained condensate simulations with multiple force fields using Python scripting. OpenABC seamlessly integrates with the OpenMM molecular dynamics engine, enabling efficient simulations with performance on a single GPU that rivals the speed achieved by hundreds of CPUs. We also provide tools that convert coarse-grained configurations to all-atom structures for atomistic simulations. We anticipate that OpenABC will significantly facilitate the adoption of in silico simulations by a broader community to investigate the structural and dynamical properties of condensates.

Fig 1. OpenABC facilitates coarse-grained and atomistic simulations of biomolecular condensates with multiple force fields.

The diagram illustrates the workflow and various functionalities of OpenABC. To set up condensate simulations, the users must provide a configuration file in the PDB format for the molecule of interest. OpenABC parses topological and structural information from the PDB file to build a molecule object. Specifying force field options allows direct simulations of individual molecules. On the other hand, the molecule object can be replicated for condensate simulations. In addition, OpenABC allows the conversion of CG configurations to atomistic structures for simulations with all-atom force fields.

Fig 2. OpenABC simplifies simulation setup with Python scripting.

The example code includes all the steps necessary for setting up and performing MD simulations of a protein condensate with MOFF and default settings in a cubic box of length 100 nm. The ten lines included in the highlight box correspond to the creation of the condensate system by parsing topological information from an initial PDB file, building a configuration file by inserting molecules into a box and incorporating the molecular objects, protein, into a container class, condensate, with appropriate force fields. The rest of the code includes standard simulation setups generic to OpenMM. We chose the Langevin middle integrator to perform simulations at 300 K with a friction coefficient of 1 ps⁻¹ and a timestep of 10 fs.

Fig 3. OpenABC integrates with OpenMM for GPU-accelerated MD simulations.

(A) Snapshots of the five systems used to benchmark simulation performance. The systems consist of N₁ HP1α dimers (blue) and N₂ 200-bp-long dsDNA (red, N₂ = 0 if not specified). The first four systems adopt homogeneous density distributions in cubic boxes of length 200 nm, while the last exhibits a dense-dilute interface in an elongated box of size 25 × 25 × 400 nm³. (B) The five data sets compare the performance of CPU simulations using GROMACS with single GPU simulations using OpenMM. The different colors indicate the number of CPUs in GROMACS simulations, as shown in the legends. The benchmarks were performed with Intel Xeon Gold 8260 CPUs and Nvidia Volta V100 GPUs.

Fig 4. OpenABC produces consistent results with a previous studying, resolving the structural differences between two HP1 homologs.

(A) Secondary structures of HP1α and HP1β along sequences. (B) Representative structures for HP1α and HP1β dimer rendered with Mol* Viewer [90]. The radii of gyration (R_g) for the two structures are 2.77 and 4.44 nm, respectively. We colored the chromodomain (CD) in orange, the chromoshadow domain (CSD) in blue, and the rest in green. (C) Probability density distributions of R_g for HP1α (red) and HP1β dimer (blue).

Fig 5. OpenABC produces phase diagrams that match previous results.

(A) Phase diagrams for HP1α (red) and HP1β (blue) dimer condensates computed with MOFF. (B) Phase diagrams for DDX4 (red) and FUS LC (blue) computed with the HPS model parameterized using the Urry hydrophobicity scale. The dots in both plots denote the density values determined from slab simulations, and the triangles represent the critical point obtained from numerical fitting.

Fig 6. OpenABC facilitates all-atom simulations by producing equilibrated initial atomistic configurations.

(A) Illustrations of the conversion from a coarse-grained configuration (top) to a fully atomistic model with explicit solvent molecules (bottom). Only 2% of water molecules and counter ions of the atomistic model are shown for clarity. The system consists of 100 HP1α dimers, and different molecules are shown in one of 25 colors. Both figures are rendered with Mol* Viewer [90]. (B) The atomistic potential energy evaluated using the CHARMM force field is shown as a function of simulation time.