**1. Introduction**

Fragment molecular orbital (FMO)-based molecular dynamics simulation (MD), hereafter referred to as "FMO-MD," is an *ab initio* MD method (Komeiji *et al.*, 2003) based on FMO, a highly parallelizable *ab initio* molecular orbital (MO) method (Kitaura *et al.*, 1999). Like any *ab initio* MD method, FMO-MD can simulate molecular phenomena involving electronic structure changes such as polarization, electron transfer, and reaction. In addition, FMO's high parallelizability enables FMO-MD to handle large molecular systems. To date, FMO-MD has been successfully applied to ion-solvent interaction and chemical reactions of organic molecules. In the near future, FMO-MD will be used to handle the dynamics of proteins and nucleic acids.

In this chapter, various aspects of FMO-MD are reviewed, including methods, applications, and future prospects. We have previously published two reviews of the method (Komeiji *et al.*, 2009b; chapter 6 of Fedorov & Kitaura, 2009), but this chapter includes the latest developments in FMO-MD and describes the most recent applications of this method.
