Usually, in a single replica scheme, each MD simulation involved in an alchemical transformation is independent of the others. Some simulation schemes, however, do not employ independent simulations schemes such as that employed by He et al., where initial structures for a simulation were obtained from snapshots of simulations from neighboring strata. Multiple replica schemes, including replica exchange and Hamiltonian exchange variants such as REST, are also utilized in the field. These schemes may increase the rate of convergence for some systems, but suffer from known issues derived from the inherent tradeoff between an enhanced sampling state and the efficient exchange of replicates. In some systems, the use of replica exchange algorithms may lead to inferior results. Another class of methods, nonequilibrium work methods utilize swarms of short simulations in which λ is driven from one extreme to the other. The free energy change of the mutation can then be calculated as a function of the nonequilibrium work. While promising for driving down the cost of computing binding free energies, these methods have not been widely adopted in the field.