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Intrinsic Viscosity of Proteins and Platonic Solids by Boundary Element Methods

2006; American Chemical Society; Volume: 2; Issue: 5 Linguagem: Inglês

10.1021/ct600062y

1549-9626

David K. Hahn, Sergio R. Aragón,

Protein purification and stability

The boundary element (BE) method is used to implement a very precise computation of the intrinsic viscosity for rigid molecules of arbitrary shape. The formulation, included in our program BEST, is tested against the analytical Simha formula for ellipsoids of revolution, and the results are essentially numerically exact. Previously unavailable, very precise results for a series of Platonic solids are also presented. The formulation includes the optional determination of the center of viscosity; however, for globular proteins, the difference compared to the computation based on the centroid is insignificant. The main application is to a series of 30 proteins ranging in molecular weight from 12 to 465 kD. The computation starts from the crystal structure as obtained from the Protein Data Bank, and a hydration thickness of 1.1 Å obtained in previous work with BEST was used. The results (extrapolated to an infinite number of triangular boundary elements) for the proteins are separated into two groups: monomeric and multimeric proteins. The agreement with experimental measurements of the intrinsic viscosity in the case of monomeric proteins is excellent and within experimental error of 5%, demonstrating that the solution and crystal structure are hydrodynamically equivalent. However, for some multimeric proteins, we observe strong systematic deviations around -20%, which we interpret as a systematic deviation of the solution structure from the crystal structure. A possible description of the structural change is deduced by using simple ellipsoid model parameters. A method to obtain intrinsic viscosity values for proteins to 1-2% accuracy (better than experimental error) on the basis of a single BE computation (avoiding the need for an extrapolation on the number of surface triangles) is also presented.