Abstract
We present OpenAWSEM and Open3SPN2, new cross-compatible implementations of coarse-grained models for protein (AWSEM) and DNA (3SPN2) molecular dynamics simulations within the OpenMM framework. These new implementations retain the chemical accuracy and intrinsic efficiency of the original models while adding GPU acceleration and the ease of forcefield modification provided by OpenMM's Custom Forces software framework. By utilizing GPUs, we achieve around a 30-fold speedup in protein and protein-DNA simulations over the existing LAMMPS-based implementations running on a single CPU core. We showcase the benefits of OpenMM's Custom Forces framework by devising and implementing two new potentials that allow us to address important aspects of protein folding and structure prediction and by testing the ability of the combined OpenAWSEM and Open3SPN2 to model protein-DNA binding. The first potential is used to describe the changes in effective interactions that occur as a protein becomes partially buried in a membrane. We also introduced an interaction to describe proteins with multiple disulfide bonds. Using simple pairwise disulfide bonding terms results in unphysical clustering of cysteine residues, posing a problem when simulating the folding of proteins with many cysteines. We now can computationally reproduce Anfinsen's early Nobel prize winning experiments by using OpenMM's Custom Forces framework to introduce a multi-body disulfide bonding term that prevents unphysical clustering. Our protein-DNA simulations show that the binding landscape is funneled towards structures that are quite similar to those found using experiments. In summary, this paper provides a simulation tool for the molecular biophysics community that is both easy to use and sufficiently efficient to simulate large proteins and large protein-DNA systems that are central to many cellular processes. These codes should facilitate the interplay between molecular simulations and cellular studies, which have been hampered by the large mismatch between the time and length scales accessible to molecular simulations and those relevant to cell biology.
Highlights
In recent decades, experimental methods for studying biological systems have made great strides providing dynamic and structural information across a range of scales
We present OpenAWSEM and Open3SPN2, two new easy-to-use and easy to modify implementations of efficient and accurate coarse-grained protein and DNA simulation forcefields that can be run hundreds of times faster than before, thereby making studies of large biomolecular machines more facile
When AWSEM was first implemented using LAMMPS 8 years ago, dynamic studies of proteins mostly focused on proteins having less than a thousand residues
Summary
Experimental methods for studying biological systems have made great strides providing dynamic and structural information across a range of scales. Retaining all of the atomic degrees of freedom gives rise to the popular all-atom models of biomolecules immersed in a solvent which is described in atomic detail. While these models are computationally costly to simulate, they can be quite accurate and have recently been used successfully to fold small proteins and even begin to allow study of the dynamics of larger systems. As parts of the biomolecule move through the solvent they are constantly buffeted by collisions with the nearby solvent molecules These collisions dramatically slow down the large scale motions that usually are of the most interest, yet in the main these frictional effects do not change the structural character of the motions
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