Abstract <p>This paper considers a generalized mathematical model of the influence of extended vortex structures (vortex wakes) on the dynamics of a mainline aircraft in cruise flight mode. The main requirement for the model is the ability to conduct a semi-naturalistic simulation of aircraft motion on flight simulators in real time. To implement the real-time mode, the paper proposes a method based on the use of artificial neural networks to approximate additional forces and moments acting on the aircraft which are caused by the influence of individual vortex segments. Calculations of transonic flow around a passenger aircraft were used to form a data set for training neural networks. The accuracy and speed of the proposed method are assessed. The article also gives an example of modeling the flight dynamics of a medium-range aircraft when entering a vortex wake of a heavy aircraft.</p>