Transport of various molecules facilitated with membrane proteins is necessary for maintaining homeostasis in living cells. In humans, dysfunction of these proteins leads to many diseases. Thus, understanding how the membrane proteins function may help using them as therapeutic targets. To successfully investigate the mechanistic aspects of transport, the choice of appropriate methods is crucial. We review the computational methods that have proven most effective in investigating transport events, specifically, deterministic time-dependent classical molecular dynamics and its enhanced sampling variants, as well as methods based on Brownian dynamics. We describe technical aspects of these methods and examples of their novel variants or combinations that have been recently and successfully applied in the transport studies. We also discuss the difficulties related to these methods and provide possible solutions to avoid them.
Keywords: Alchemical free energy calculations; Brownian dynamics; Conformational dynamics; Enhanced sampling methods; Membrane channels; Molecular dynamics simulations; Substrate binding and permeation; Transport through membranes; Transporters and pumps.