Building Water Models: A Different Approach

Overview

Journal J Phys Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2014 Nov 18

PMID 25400877

Citations 372

Authors

Saeed Izadi

Ramu Anandakrishnan

Alexey V Onufriev

Affiliations

Soon will be listed here.

Abstract

Simplified classical water models are currently an indispensable component in practical atomistic simulations. Yet, despite several decades of intense research, these models are still far from perfect. Presented here is an alternative approach to constructing widely used point charge water models. In contrast to the conventional approach, we do not impose any geometry constraints on the model other than the symmetry. Instead, we optimize the distribution of point charges to best describe the "electrostatics" of the water molecule. The resulting "optimal" 3-charge, 4-point rigid water model (OPC) reproduces a comprehensive set of bulk properties significantly more accurately than commonly used rigid models: average error relative to experiment is 0.76%. Close agreement with experiment holds over a wide range of temperatures. The improvements in the proposed model extend beyond bulk properties: compared to common rigid models, predicted hydration free energies of small molecules using OPC are uniformly closer to experiment, with root-mean-square error <1 kcal/mol.

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References

Rajamani S, Ghosh T, Garde S . Size dependent ion hydration, its asymmetry, and convergence to macroscopic behavior. J Chem Phys. 2004; 120(9):4457-66. DOI: 10.1063/1.1644536. View

Skinner L, Huang C, Schlesinger D, Pettersson L, Nilsson A, Benmore C . Benchmark oxygen-oxygen pair-distribution function of ambient water from x-ray diffraction measurements with a wide Q-range. J Chem Phys. 2013; 138(7):074506. DOI: 10.1063/1.4790861. View

Pronk S, Pall S, Schulz R, Larsson P, Bjelkmar P, Apostolov R . GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013; 29(7):845-54. PMC: 3605599. DOI: 10.1093/bioinformatics/btt055. View

Wang J, Wolf R, Caldwell J, Kollman P, Case D . Development and testing of a general amber force field. J Comput Chem. 2004; 25(9):1157-74. DOI: 10.1002/jcc.20035. View

Gilson M, Zhou H . Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct. 2007; 36:21-42. DOI: 10.1146/annurev.biophys.36.040306.132550. View

Rick S . A reoptimization of the five-site water potential (TIP5P) for use with Ewald sums. J Chem Phys. 2004; 120(13):6085-93. DOI: 10.1063/1.1652434. View

Akin-Ojo O, Wang F . The quest for the best nonpolarizable water model from the adaptive force matching method. J Comput Chem. 2010; 32(3):453-62. DOI: 10.1002/jcc.21634. View

Fennell C, Li L, Dill K . Simple liquid models with corrected dielectric constants. J Phys Chem B. 2012; 116(23):6936-44. PMC: 3729351. DOI: 10.1021/jp3002383. View

Mobley D, Baker J, Barber 2nd A, Fennell C, Dill K . Charge asymmetries in hydration of polar solutes. J Phys Chem B. 2008; 112(8):2405-14. PMC: 2745216. DOI: 10.1021/jp709958f. View

10.

Kramer C, Spinn A, Liedl K . Charge Anisotropy: Where Atomic Multipoles Matter Most. J Chem Theory Comput. 2015; 10(10):4488-96. DOI: 10.1021/ct5005565. View

11.

Vega C, Abascal J . Simulating water with rigid non-polarizable models: a general perspective. Phys Chem Chem Phys. 2011; 13(44):19663-88. DOI: 10.1039/c1cp22168j. View

12.

Ichiye T, Tan M . Soft sticky dipole-quadrupole-octupole potential energy function for liquid water: an approximate moment expansion. J Chem Phys. 2006; 124(13):134504. DOI: 10.1063/1.2161201. View

13.

Fuentes-Azcatl R, Alejandre J . Non-polarizable force field of water based on the dielectric constant: TIP4P/ε. J Phys Chem B. 2014; 118(5):1263-72. DOI: 10.1021/jp410865y. View

14.

Wu Y, Tepper H, Voth G . Flexible simple point-charge water model with improved liquid-state properties. J Chem Phys. 2006; 124(2):024503. DOI: 10.1063/1.2136877. View

15.

Abascal J, Vega C . A general purpose model for the condensed phases of water: TIP4P/2005. J Chem Phys. 2006; 123(23):234505. DOI: 10.1063/1.2121687. View

16.

Rusnak A, Pinnick E, Calderon C, Wang F . Static dielectric constants and molecular dipole distributions of liquid water and ice-Ih investigated by the PAW-PBE exchange-correlation functional. J Chem Phys. 2012; 137(3):034510. DOI: 10.1063/1.4734594. View

17.

Mobley D, Bayly C, Cooper M, Shirts M, Dill K . Small molecule hydration free energies in explicit solvent: An extensive test of fixed-charge atomistic simulations. J Chem Theory Comput. 2010; 5(2):350-358. PMC: 2701304. DOI: 10.1021/ct800409d. View

18.

Case D, Cheatham 3rd T, Darden T, Gohlke H, Luo R, Merz Jr K . The Amber biomolecular simulation programs. J Comput Chem. 2005; 26(16):1668-88. PMC: 1989667. DOI: 10.1002/jcc.20290. View

19.

Dill K, Truskett T, Vlachy V, Hribar-Lee B . Modeling water, the hydrophobic effect, and ion solvation. Annu Rev Biophys Biomol Struct. 2005; 34:173-99. DOI: 10.1146/annurev.biophys.34.040204.144517. View

20.

Anandakrishnan R, Baker C, Izadi S, Onufriev A . Point charges optimally placed to represent the multipole expansion of charge distributions. PLoS One. 2013; 8(7):e67715. PMC: 3701554. DOI: 10.1371/journal.pone.0067715. View