**4. Prospects and conclusion**

As reviewed so far, FMO-MD has been applied to various chemical phenomena in the presence of explicit solvents and has given realistic molecular pictures of the phenomena. We are planning to extend the field of FMO-MD by introduction of new capabilities, as follows.

The so-called QM/MM scheme will enhance the target size of FMO-MD. QM/MM has attracted great interest in simulating condensed-phase systems as well as proteins. In this scheme, the chemically relevant region is subjected to QM calculations while the environmental effects are incorporated through a set of MM parameters. MFMO has a conceptual similarity to QM/MM, and hence we have a plan to implement a general QM/MM ability in conjunction with MFMO.

The improvement of accuracy in FMO gradient evaluations may be a future subject. Nagata's reformulation, including the supplemental response terms of monomers (Nagata *et al.*, 2011a) as well as the BDA-related residual contributions (Nagata *et al.,* 2010), are of interest for implementation at the HF level.

Another important issue is the extraction of more information from FMO-MD trajectories. From a series of configurations, the time-dependent fluctuations in electronic densities can be derived, some of which are correlated with the creation and destruction of bonding interactions. For example, the Fourier transform-based analyses may shed light on the detailed dynamical picture of nucleophilic attack reactions.

In conclusion, FMO-MD is a highly-parallelizable *ab initio* MD method. FMO-MD has advanced rapidly by improvement of both the FMO and MD portions of the method and has been successfully applied to various chemical phenomena in solution. We are planning to extend the methodology and application of FMO-MD by incorporating several new features.
