New Born Radii Deriving Method for Generalized Born Model

Here we report a method to calculate Born radii, an important parameter used in a Generalized Born model. Traditional methods to derive Born radii are mostly based on a complicated formula, while our method is easier and more direct. Atoms are classified according to their atom type, and the Born radii of each type are obtained by fitting to experimental solvation free energy. The SMARTS language is used for the exact definition of atoms types, and Ullmann's subgraph isomorphism algorithm is used to deduce the environment. A generic algorithm is used for the parameter fitting because of its efficiency in searching a huge phase space, and its results are then optimized by using the conjugate gradient method. The final parameter set is fitting from a training set containing 357 molecules and is tested using a test set of 44 small organic molecules, and the average error is 0.58 kcal/mol for 36 neutral molecules and is 1.67 kcal/mol for 8 ions. The model is further tested under organic molecules, biopolymers, and a protein-inhibitor complex and yields reliable results in all these cases. This method can be used to accelerate molecular docking calculations.

[1]  Martin Karplus,et al.  SOLVATION. A MOLECULAR DYNAMICS STUDY OF A DIPEPTIDE IN WATER. , 1979 .

[2]  C. Cramer,et al.  General parameterized SCF model for free energies of solvation in aqueous solution , 1991 .

[3]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[4]  Harold A. Scheraga,et al.  Free energies of hydration of solute molecules. 1. Improvement of the hydration shell model by exact computations of overlapping volumes , 1987 .

[5]  K. Sharp,et al.  Macroscopic models of aqueous solutions : biological and chemical applications , 1993 .

[6]  Wei Zhang,et al.  Parameters for the generalized Born model consistent with RESP atomic partial charge assignment protocol , 2003 .

[7]  B. Honig,et al.  Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis , 1988, Proteins.

[8]  W. C. Still,et al.  Semianalytical treatment of solvation for molecular mechanics and dynamics , 1990 .

[9]  Gregory D. Hawkins,et al.  Parametrized Models of Aqueous Free Energies of Solvation Based on Pairwise Descreening of Solute Atomic Charges from a Dielectric Medium , 1996 .

[10]  Julian R. Ullmann,et al.  An Algorithm for Subgraph Isomorphism , 1976, J. ACM.

[11]  K. Sharp,et al.  Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models , 1994 .

[12]  Jiang Zhu,et al.  Parametrization of a Generalized Born/Solvent-Accessible Surface Area Model and Applications to the Simulation of Protein Dynamics , 2002 .

[13]  K M Merz,et al.  GB/SA water model for the Merck molecular force field (MMFF). , 2000, Journal of molecular graphics & modelling.

[14]  Bhyravabhotla Jayaram,et al.  Solvation Free Energy of Biomacromolecules: Parameters for a Modified Generalized Born Model Consistent with the AMBER Force Field , 1998 .

[15]  A. D. McLachlan,et al.  Solvation energy in protein folding and binding , 1986, Nature.

[16]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.

[17]  David A. Case,et al.  Effective Born radii in the generalized Born approximation: The importance of being perfect , 2002, J. Comput. Chem..

[18]  W. C. Still,et al.  The GB/SA Continuum Model for Solvation. A Fast Analytical Method for the Calculation of Approximate Born Radii , 1997 .

[19]  Tingjun Hou,et al.  Some Basic Data Structures and Algorithms for Chemical Generic Programming , 2004, J. Chem. Inf. Model..

[20]  Harold A. Scheraga,et al.  Free energies of hydration of solute molecules. 3. Application of the hydration shell model to charged organic molecules , 1987 .

[21]  H. Scheraga,et al.  Accessible surface areas as a measure of the thermodynamic parameters of hydration of peptides. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Karplus,et al.  A Comprehensive Analytical Treatment of Continuum Electrostatics , 1996 .

[23]  W. L. Jorgensen,et al.  Monte Carlo simulation of differences in free energies of hydration , 1985 .