Sequential QM/MM

ASEP/MD, acronym for average solvent electrostatic potential obtained from molecular dynamics data, is a sequential QM/MM method that makes extensive use of the mean field approximation (MFA) [24], In solution, any static property A of the system must be calculated by averaging over the configurational space A defined by all the configurations thermally accessible to the system ... 

THE SEQUENTIAL QM/MM METHOD AND ITS APPLICATIONS TO SOLVENT EFFECTS IN ELECTRONIC AND STRUCTURAL PROPERTIES OF SOLUTES... 

The idea of the sequential QM/MM method is thus to join the quantum calculations and the computer simulations in an efficient way to reduce the number of QM calculations and hence the computational cost. Therefore, in the two-stage procedure the system is first simulated using classical force fields for all interactions,... 

Since the suggestion of the sequential QM/MM hybrid method, Canuto, Coutinho and co-authors have applied this method with success in the study of several systems and properties shift of the electronic absorption spectrum of benzene [42], pyrimidine [51] and (3-carotene [47] in several solvents shift of the ortho-betaine in water [52] shift of the electronic absorption and emission spectrum of formaldehyde in water [53] and acetone in water [54] hydrogen interaction energy of pyridine [46] and guanine-cytosine in water [55] differential solvation of phenol and phenoxy radical in different solvents [56,57] hydrated electron [58] dipole polarizability of F in water [59] tautomeric equilibrium of 2-mercaptopyridine in water [60] NMR chemical shifts in liquid water [61] electron affinity and ionization potential of liquid water [62] and liquid ammonia [35] dipole polarizability of atomic liquids [63] etc. 

On the other hand, for polar molecules in polar environments, this approach may lead to errors because the actual polarization of the molecule may significantly surpass any modest estimate (e.g., 20%) and the extra polarization may be responsible for important differences in the solute-solvent interaction. Hence, one needs a strategy to account more systematically for the solute polarization. It would be especially interesting to do it in a way to preserve the main advantage of the sequential QM/MM methodology, that is, performing only statistically relevant QM calculations. 

A sequential QM/MM methodology was applied to study the magnetic shielding constants of hydrated pyridine. In this approach, the liquid configuration is generated first by classical MC simulations. After that, a subset of uncorrelated configurations is sampled and submitted to QM calculations. The MC simulations were carried out in the NPT... 

Gester RM et al (2009) NMR chemical shielding and spin-spin coupling constants of liquid NH3 a systematic investigation using the sequential QM/MM method. J Phys Chem A 113 14936-14942... 

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