Eukaryotic cytochromes P450 (P450) are membrane bound enzymes oxidizing a broad spectrum of hydrophobic substrates including xenobiotics. Protein–protein interactions play a critical role in this process. In particular, the formation of transient complexes of P450 with another protein of the endoplasmic reticulum membrane, cytochrome b5 (cyt b5), dictates catalytic activities of several P450s. To lay structural foundation for the investigation of these effects we used microsecond all-atom molecular dynamics (MD) simulations to identify three stable binding modes (sAI, sAII, and sB) between soluble domains of human P450 1A2 and cyt b5 in aqueous solution, and examined these binding modes in the full-length complex (mAI, mAII, and mB) using multi-scale modeling techniques. The membrane-spanning transmembrane domains of both proteins were spontaneously assembled from the protein/phospholipid/water mixture using coarse-grained MARTINI force field, and the full-length complexes representing all three binding modes in the solvated dilauroylphosphatidylcholine bilayer were simulated using all-atom MD. The X-shaped contact between antiparallel transmembrane domains of P450 1A2 and cyt b5 that was established during the coarse-grained MD was preserved in the all-atom MD. In the membrane environment, modes mAI and mB were retained in essentially unchanged form, whereas the mAII mode was excluded as topologically impossible. The mutual position of domains in binding mode mAI is analogous to the most favorable structure of the P450 1A2 - cyt b5 complex identified previously for soluble domains. Featuring the largest contact area, the smallest structural flexibility, the shortest electron transfer distance and the largest number of inter-protein salt bridges, the mAI mode is the best candidate for the catalytically relevant full-length complex.