Polarization is an important component to include in biomolecular simulations, as it can account for changes in electrostatic environment and behavior in asymmetric environments, such as proteins. Being a many-body effect, however, polarization is often computationally expensive to implement, primarily due to the need to solve for induced dipoles to self-consistency. We have developed a modification to the AMOEBA polarizable force field to improve computational efficiency by eliminating the expensive iterative calculation. We are also applying the AMOEBA force field to protein protonation free energy calculations, as the shortcomings of fixed-charge models in such calculations have been demonstrated previously, particularly in the determination of protonation free energies of titratable functional groups in buried residues.The AMOEBA force field includes a sophisticated treatment of electrostatics, using a multipole expansion through the quadrupole and polarization via point inducible dipoles[1]. We will present a modification of the AMOEBA force field using Drude oscillators to model polarization in an attempt to increase computational efficiency. The Drude oscillator model is a charge attached to each atomic center with a harmonic spring whose deviation and direction determines the polarization. We avoid self-consistent iteration using a �cold� thermostat via an extended Lagrangian method in order to eliminate the expensive self-consistent iteration of point inducible dipole[2].We are applying the AMOEBA polarizable force field to the calculation of the free energy changes of protonation of ionizable residues in staphylococcal nuclease ?+PHS mutant. This mutant has a wealth of experimental pKa data available[3] and provides a benchmark for computational methods. We seek to determine if the use of a force field that includes polarization can improve the calculation of protonation free energies and thus pKacalculations.[1] Ponder, J. W. et al. J. Phys. Chem. B 2010  , 114, 2549-2564[2] Lamoureux, G.; Roux, B. J. Chem. Phys. 2003  , 119, 3025-3039[3] Casta�eda, C. A. et al. Proteins 2009  , 77, 570-588

Increasing the efficiency of the AMOEBA force field using Drude oscillators and application to protein pK<sub>a</sub> calculations

248th National Meeting (2014)

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Increasing the efficiency of the AMOEBA force field using Drude oscillators and application to protein pKa calculations

Increasing the efficiency of the AMOEBA force field using Drude oscillators and application to protein pK_a calculations