Table 2.

Location of the four major access channels of CYP3A4. ${}^a$ According to the authors of [60,69]: C (closed conformation), O1 (conformation opened, in block 1), O2 (conformation opened, in block 2; opening of O2 is larger than opening of O1). ${}^b$ The triangulations of the channels performed with CCCPP can be described with lengthy technical details that we consider to be non essential in this paper, such as the lining atoms and residues: see these latter in Table 3.10 in [69]. ${}^c$ Substrate recognition sites (SRS), according to the authors of [70]. ${}^d$ Depending on the ligand size, channel 2f can offer a larger opening than channel 2a.

Channel	Block	Conformation ${}^{\mathit{a}}$	Exit Location	Exit Location	SRS ${}^{\mathit{c}}$
			In the CYP ${}^{\mathit{b}}$	Outside the CYP
2a	1	C, O1, O2	Between F-G and B-C loops	Plasma membrane	1, 2, 3
			and ${\beta }_1$ sheet	(PM)
2f ${}^d$	2	O2	Between helix F/F-G loop	Interface	2, 6
			and C-terminal loop	PM/cytosol
S	2	O2	Between helices E,F,I	Cytosol	4, 6
			and C-terminal loop
2e		C, O1, O2	Through B-C loop	Cytosol	1