Simulation of Chemical Reactions in Solution

Microscopic simulations of chemical reactions in solution were pioneered in Warshel's work1. This included the use of molecular dynamics to evaluate the activation free energies of chemical reactions in solution, developing the microscopic equivalent of Marcus' parabolas for electron transfer reactions2,3, and introducing the practical microscopic simulations of Dispersed Polaron approach for simulating nuclear tunneling effects in electron transfer reactions. This Dispersed Polaron approach is sometime known as the Spin-Boson model. We were also the first that implemented path integral centroid methods in simulating chemical reactions in solutions and enzymes (see 4 and 5). Our "work horse" in the studies of chemical reactions in solution has been the EVB method. This method, which is now used widely by other research groups (see 6), provided for the first time a correct coupling between the solute Hamiltonian and the solvent field and allows us to evaluate nonequilibrium solvation effets in a consistent way. The EVB also provides what is at present the most consistent way of transferring ab initio gas phase potential surfaces to solution. We also made significant advances in pioneering QM/MM studies of chemical reactions in solution7. Our progress in this direction is now focused on approaches that couple the Langevin Dipole (LD) model with ab initio methods8 and in using the EVB model as a reference potential for ab initio QM/MM simulations9 and on EVB driven ab initio simulations of all-atom solvent models.

More recently, with the emergence of more computer power we started to use ab initio QM/MM (QM(ai)/MM) methods with the EVB as a reference potential, which we named paradynamics (PD)10 in studies of chemical reactions in solutions. We also advanced in evaluating the QM(ai)/MM free energy surfaces in solution reactions that serve as reference reactions for key biological processes (e.g. 11). Overall a major part of our current studies of reactions in solution is focused on constructing the reference reactions for biological reactions.

  • Electron and Proton Transfer reactions
  • Studies of Linear Free Energy Relationship (LFER)
  • Sn2 and Sn1 Reactions
  • Organometallic Systems
  • Phosphate Hydrolysis
      coordinate files used with molaris: 1w_pt_ts 2w_pt_ts

(A) The free energy surface in the R1, R2 space for the first step of the phosphate monoester hydrolysis (the cleavage of the P-O bond) in solution. The system is modeled by considering the hydrolysis of MDP using B3LYP functional with 6-31G(d) basis for P and 6-31G for other elements, with a QM region (see inset) that includes the MDP plus Mg+2 ion and 6 QM H2O 16x16 10 ps QM/MM trajectories. (B) The surface for the 2W PT step (PT from the attacking water to the 2W at the TS/Plateau), showing that this step occurs spontaneously near TS1. Here ΞΎ is the 2W PT coordinate, defined as the difference between the proton-donor and proton-acceptor distances. Further details about the definition and construction of the PT coordinate are discussed in Ref. 5. The corresponding surfaces for the case without Mg+2 are given in Fig S1.

See also movie