An analytical approach to computing biomolecular electrostatic potential. II. Validation and applications

摘要

An ability to efficiently compute the electrostatic potential produced by molecular charge distributions under realistic solvation conditions is essential for a variety of applications. Here, the simple closed-form analytical approximation to the Poisson equation rigorously derived in Part I for idealized spherical geometry is tested on realistic shapes. The effects of mobile ions are included at the Debye-Huckel level. The accuracy of the resulting closed-form expressions for electrostatic potential is assessed through comparisons with numerical Poisson-Boltzmann (NPB) reference solutions on a test set of 580 representative biomolecular structures under typical conditions of aqueous solvation. For each structure, the deviation from the reference is computed for a large number of test points placed near the dielectric boundary (molecular surface). The accuracy of the approximation, averaged over all test points in each structure, is within 0.6 kcal/mol/vertical bar e vertical bar similar to kT per unit charge for all structures in the test set. For 91.5% of the individual test points, the deviation from the NPB potential is within 0.6 kcal/mol/vertical bar e vertical bar. The deviations from the reference decrease with increasing distance from the dielectric boundary: The approximation is asymptotically exact far away from the source charges. Deviation of the overall shape of a structure from ideal spherical does not, by itself, appear to necessitate decreased accuracy of the approximation. The largest deviations from the NPB reference are found inside very deep and narrow indentations that occur on the dielectric boundaries of some structures. The dimensions of these pockets of locally highly negative curvature are comparable to the size of a water molecule; the applicability of a continuum dielectric models in these regions is discussed. The maximum deviations from the NPB are reduced substantially when the boundary is smoothed by using a larger probe radius (3 angstrom) to generate the molecular surface. A detailed accuracy analysis is presented for several proteins of various shapes, including lysozyme whose surface features a functionally relevant region of negative curvature. The proposed analytical model is computationally inexpensive; this strength of the approach is demonstrated by computing and analyzing the electrostatic potential generated by a full capsid of the tobacco ring spot virus at atomic resolution (500 000 atoms). An analysis of the electrostatic potential of the inner surface of the capsid reveals what might be a RNA binding pocket. These results are generated with the modest computational power of a desktop personal computer. (c) 2008 American Institute of Physics.