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MSC'99 Seminar D6: Friday, 19 March 1999, 11:05 am

Continuum Solvent Methods for Quantum Mechanics,

Molecular Dynamics and Monte Carlo Simulations

Daniel T. Mainz & William A. Goddard III

Materials and Process Simulation Center, Caltech, Pasadena, CA 91125

Presentation Materials:

Abstract:

Solvation effects are of tremendous importance to molecular simulation, and are a primary research concern at the MSC, where several collaborators are studying peptide folding statistics, novel dendritic polymer structures and functionalities, and developing new force fields based on quantum chemistry results in solution. Several methods of including solvation effects in ab initio quantum mechanics and classical molecular dynamics will be addressed, including explicit solvent studies and force field parameterizations. The argument is made that continuum dielectric methods best balance the competing needs for acceptable accuracy and computational efficiency. The use of the Poisson-Boltzmann equation for solvation, based on Debye-Hückel theory, is presented, and serves as the foundation for computational packages which use finite element approaches (PBF) and Generalized Born (GB) algorithms. PBF works exceptionally well with ab initio programs, yielding solvation free energies within 0.4 kcal/mol at little additional cost to a gas-phase calculation. Because it is a faster algorithm, GB methods are a better fit for molecular dynamics simulations with the MSC-developed program MPSim. The S-GB program significantly improves upon the GB formulation; in addition to being faster and scaling better with system size, it reduces absolute energetic errors from 10% of the total energy of ribonuclease A conformers obtained through standard GB methods to only 1% error. S-GB is especially amenable to computational parallelization; this shall bring solvated dynamical simulations with MPSim to be only marginally more expensive than solute-only calculations.

Funding: ARO/MURI, NSF Chemistry

Figure 1: The physical picture of continuum solvent methods. All of the solvent atoms are eliminated from the system, and replaced with a dielectric continnum; the electrostatic effects are governed by the Poisson-Boltzmann equation.

   

GBSA

S-GB

Chain length

Natoms

Abs. error

Rel. sq. error

Abs. error

Rel sq. error

4

58

10.229

9.137

2.027

6.273

18

280

23.703

38.811

2.213

22.869

22

362

45.414

22.278

2.931

1.891

30

620

65.929

37.954

10.801

8.946

Table 1: (from Ghosh, et al.) Comparison of conventional GB model with new S-GB method for peptides of different lengths. S-GB is markedly better at achieving accurate absolute and relative energies with respect to high-quality numerical solution of the PB equation.

References: