title: Evaluating the dynamics and electrostatic interactions of folded proteins in implicit solvents.
abstract: Three implicit solvent models, namely GBMVII, FACTS, and SCPISM, were evaluated for their abilities to emulate an explicit solvent environment by comparing the simulated conformational ensembles, dynamics, and electrostatic interactions of the Src SH2 domain and the Lyn kinase domain. This assessment in terms of structural features in folded proteins expands upon the use of hydration energy as a metric for comparison. All-against-all rms coordinate deviation, average positional fluctuations, and ion-pair distance distribution were used to compare the implicit solvent models with the TIP3P explicit solvent model. Our study shows that the Src SH2 domains solvated with TIP3P, GBMVII, and FACTS sample similar global conformations. Additionally, the Src SH2 ion-pair distance distributions of solvent-exposed side chains corresponding to TIP3P, GBMVII, and FACTS do not differ substantially, indicating that GBMVII and FACTS are capable of modeling these electrostatic interactions. The ion-pair distance distributions of SCPISM are distinct from others, demonstrating that these electrostatic interactions are not adequately reproduced with the SCPISM model. On the other hand, for the Lyn kinase domain, a non-globular protein with bilobal structure and a large concavity on the surface, implicit solvent does not accurately model solvation to faithfully reproduce partially buried electrostatic interactions and lobe-lobe conformations. Our work reveals that local structure and dynamics of small, globular proteins are modeled well using FACTS and GBMVII. Nonetheless, global conformations and electrostatic interactions in concavities of multi-lobal proteins resulting from simulations with implicit solvent models do not match those obtained from explicit water simulations.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Markey Center for Structural Biology, and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, 47907.
authors.forename: Duy P
authors.initials: DP
authors.lastname: Hua
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Markey Center for Structural Biology, and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, 47907.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Markey Center for Structural Biology, and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, 47907.
authors.forename: Amitava
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Markey Center for Structural Biology, and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, 47907.
authors.forename: Carol Beth
authors.initials: CB
authors.lastname: Post
mesh_terms: D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry*; D055672:Static Electricity; D019061:src-Family Kinases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012997:Solvents; D019061:src-Family Kinases
keywords: CHARMM; Src-family kinase; all-against-all rmsd; solvation methods; time-development rms fluctuation