SMOG 2 and OpenSMOG: Extending the limits of structure-based models

Abstract

Applying simulations with structure-based (Go-like) models has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular interactions are explicitly defined to stabilize an experimentally-determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structure-based (i.e. SMOG) models for any type of polymer-ligand system. Since its original release, user feedback has driven the implementation of numerous enhancements. Here, we describe recent extensions to the software and demonstrate the capabilities of the most recent version, SMOG v2.4. Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.0). To illustrate the utility of these advances, we present several applications of SMOG2 and OpenSMOG, which include systems with millions of atoms, long polymers and explicit ions. We also highlight how one can incorporate non-structure-based (e.g. AMBER-based) energetics to define a hybrid class of models. The representative applications include large-scale rearrangements of the SARS-CoV-2 Spike protein, the HIV-1 capsid in the presence of explicit ions, and crystallographic lattices of ribosomes and proteins. In summary, SMOG 2 and OpenSMOG provide robust support for researchers who seek to apply structure-based models to large and/or intricate biomolecular systems.

Small Neutral Crowding Solute Effects on Protein Folding Thermodynamic Stability and Kinetics

“…Molecular dynamics was performed using the widely employed structure-based model (SBM), and proteins were coarse-grained in a C α atom level of simplification (Figure ). In this model, individual beads centered at the α carbon position are used to represent the residue atoms of proteins. − The Hamiltonian equation that represents the protein beads interactions is constructed based on the geometry of the protein native structure, and this potential has its minimum at this reference state. − The potential energy in a configuration Γ, calculated relative to the configuration of the native structure Γ o , is given by with ϵ r = 100ϵ C , ϵ θ = 20ϵ C , ϵ ϕ = ϵ C , and ϵ NC = ϵ C , in which ϵ C is the interaction energy per contact equal to 1.0 in reduced units. r , θ, and ϕ represent the distance between two subsequent residues, the angles formed by three and four subsequent residues of native structure, respectively.…”

Diffuse ions coordinate dynamics in a ribonucleoprotein assembly

“…S12), and they can be performed effectively using modern GPU resources. 101 With these levels of performance, modest-sized compute clusters are sufficient to perform simulations that describe millisecond effective timescales for MDa-scale assemblies. Accordingly, it is now becoming feasible to explore the impact of ions on large-scale conformational rearrangements.…”