Combining coarse‐grained nonbonded and atomistic bonded interactions for protein modeling

Abstract

A hybrid coarse-grained (CG) and atomistic (AT) model for protein simulations and rapid searching and refinement of peptide-protein complexes has been developed. In contrast to other hybrid models that typically represent spatially separate parts of a protein by either a CG or an AT force field model, the present approach simultaneously represents the protein by an AT (united atom) and a CG model. The interactions of the protein main chain are described based on the united atom force field allowing a realistic representation of protein secondary structures. In addition, the AT description of all other bonded interactions keeps the protein compatible with a realistic bonded geometry. Nonbonded interactions between side chains and side chains and main chain are calculated at the level of a CG model using a knowledge-based potential. Unrestrained molecular dynamics simulations on several test proteins resulted in trajectories in reasonable agreement with the corresponding experimental structures. Applications to the refinement of docked peptide-protein complexes resulted in improved complex structures. Application to the rapid refinement of docked protein-protein complex is also possible but requires further optimization of force field parameters.

Flexible docking and refinement with a coarse‐grained protein model using ATTRACT

“…The mixed atomistic/CG model employed for flexible refinement of docked complexes has been described in detail elsewhere . Briefly, the GROMOS united atom force field with modifications was used for controlling the bonded geometry.…”

“…A systematic docking search typically yields many putative complexes that need to be translated to atomic resolution and frequently require further structural refinement and rescoring. Recently, we introduced a rapid flexible refinement procedure based on a mixed fully flexible atomistic description of the bonded geometry of the protein partners and a CG‐virtual site representation of the nonbonded interaction equivalent to the CG model used during systematic docking . This model still results in a smooth representation of the protein surfaces (due to the CG model for nonbonded interactions) which is a prerequisite for substantial translational and rotational rearrangements of the protein partners during limited simulation times.…”

New Strategies for Integrative Dynamic Modeling of Macromolecular Assembly

“…In this context, a hybrid CG/atomistic model using implicit solvent to speed up calculations has been recently proposed by Zacharias (2013). This model was successfully used to study the self-assembly process of the axin-peptide-ADC receptor system and the α-helical p53 peptide binding to the MDM2 receptor protein.…”

Recent Advances in Transferable Coarse-Grained Modeling of Proteins

“…Zacharias et al recently developed a multi-scale AA/CG model 150 by combing a modified GROMOS united atom force field with the ATTRACT 151 CG model for studying protein-protein interactions. In this model, bonded interactions are generic and are described by atomistic force field while non-bonded interactions are calculated via CG terms.…”