Pragmatic Coarse-Graining of Proteins: Models and Applications

Abstract

The molecular details involved in the folding, dynamics, organization, and interaction of proteins with other molecules are often difficult to assess by experimental techniques. Consequently, computational models play an ever-increasing role in the field. However, biological processes involving large-scale protein assemblies or long time scale dynamics are still computationally expensive to study in atomistic detail. For these applications, employing coarse-grained (CG) modeling approaches has become a key strategy. In this Review, we provide an overview of what we call pragmatic CG protein models, which are strategies combining, at least in part, a physics-based implementation and a top-down experimental approach to their parametrization. In particular, we focus on CG models in which most protein residues are represented by at least two beads, allowing these models to retain some degree of chemical specificity. A description of the main modern pragmatic protein CG models is provided, including a review of the most recent applications and an outlook on future perspectives in the field.

SIRAH Late Harvest: Coarse-Grained Models for Protein Glycosylation

“…The first step in running a simulation with SIRAH is to map an atomistic structure to its CG representation. This procedure is performed using a script provided in the SIRAH package. , A correct mapping absolutely requires residue names to be written according to the GLYCAM nomenclature. It is important to emphasize that our CG model requires the position of the hydrogen atoms in the atomistic structure.…”

“…For instance, the intricate glycosylation pattern recently reported for the Spike protein of SARS-CoV-2 53 is perfectly amenable to the set of CG parameters reported here. Owing to the pragmatic nature of our force field, 60 generating a general recipe for arbitrary topologies for new residues, for instance, furanoses, might not be straightforward. Nevertheless, the availability parameter files (https://github.com/SIRAHFF) and the information reported in the Supporting Information (Figure S1 and Tables S1−S3) can provide general rules for creating CG parameters for other glycans.…”

Toward Consistent Physics-Based Modeling of Local Backbone Structures and Chirality Change of Proteins in Coarse-Grained Approaches

“…Backbone-local interactions are very likely to presculpt the protein free-energy landscape to favor regular helix and sheet structures . Therefore, the development of local-interaction-energy terms in both all-atom − and coarse-grained − force fields has received a lot of attention. The torsional and improper-torsional terms that describe the energy of rotation about a bond (in all-atom models) or about a virtual bond (in coarse-grained models) or the geometry of the surrounding of a central atom or site, respectively, are particularly important because a dihedral angle is a collective reaction coordinate that describes the concerted motion of four atoms or sites.…”

All-Atom Biomolecular Simulation in the Exascale Era

“…Other recent reviews and perspectives − have discussed extensively the current status of biomolecular simulation and modeling, including coarse-grained methods . Here, we focus on atomic-level simulations and both the enormous potential and the resulting challenges created by the emergence of exascale computing.…”