title: Coarse-grained simulations of protein-protein association: an energy landscape perspective.
abstract: Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes.
authors.affiliation: Center for Proteomics and Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Krishnakumar M
authors.initials: KM
authors.lastname: Ravikumar
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Sichun
authors.initials: S
authors.lastname: Yang
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D011506:Proteins