MSC 2000 Seminar: Thursday, 23 March 2000, 1:40 pm

Solvation in Molecular Dynamics and Quantum Chemistry

**Daniel T. Mainz** & William A. Goddard III

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

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. Discussed along with the
key simulation programs in development by our group, including Jaguar (QM)
and MPSim (parallel MD), several methods to include solvation will be
addressed. Of these, continuum dielectric methods best balance the
competing needs for acceptable accuracy and computational efficiency. The
use of the Poisson-Boltzmann equation for solvation 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. The S-GB program significantly improves
upon the GB formulation; in addition to being faster and scaling better
with system size, it is especially amenable to computational
parallelization; this shall bring solvated dynamical simulations with MPSim
to be only marginally more expensive than solute-only
calculations. Finally, methods to bring quantum mechanics, molecular
mechanics, and continuum solvation together in complex QM/MM simulations
will be discussed. These calculations, presently underway, are the
beginnings of true hierarchical simulation methods of significant
importance to the MSC's research purposes.

**Funding:** DOE/ASCI-ASAP** **

**Figure 1:** Parallel scaling of MPSim on a half-million atom structure
of a common rhinovirus using SGI Origin2000 machines up to 64
processors. The red line shows the inferior
scaling of level 5 octree decomposition, compared to the blue line's scaling of level 6 decomposition.

**Figure 2**: QM/MM schematic for calculating condensed-phase
structures, vibrational frequencies, and relative energies of minimum and
transition state structures of RDX, a high-explosive. The green atoms are calculated with Jaguar, the others
with IMPACT or MPSim, and all the atoms are surrounded by a continuum
solvent evaluated with PBF.

**References**:

- SCRF methods: Tannor, et al., JACS,
**116**, 11875 (1994) - PB Solvation: Cortis, et al.,
J. Comput. Chem.
**18**, 1591 (1997) - GB Solvation: Ghosh, et al.,
J. Phys. Chem. B.
**102**, 19083 (1998) - MPSim: Lim, et al.,
J. Comput. Chem.
**18**, 501 (1997)