In this work 54 ligand transformations for 5 diverse protein targets: MCL1, PTP1B, TYK2, CDK2 and thrombin have been examined and relative binding free energy calculations performed using three MD packages NAMD2, NAMD3 and OpenMM. Analysis of these calculations was made using two free energy estimators: TI and FEP. Effort was made to match the alchemical methodologies between MD packages as closely as possible. However, differences were observed such as diverse soft-core parameters, λ schedules, methods for calculating the TI gradient and the use of either decoupling or annihilating methods to turn off the alchemical regions. Despite these differences, the results show good agreement between molecular dynamics packages with an average mean unsigned error between packages of 0.5 kcal/mol.