What @trurl is talking about your system/appdata is on your array not on your SSD aka what most of us refer to as your Cache drive.
By keeping your dockers and VM's on your SSD/Cache drive set to Only it will keep your VM's, Docker files on your SSD/Cache so it doesn't spin up your drives when it checks and does things. It will also increase your load speeds of Plex by a HUGE margin because it doesn't have to spin up drives to display thumbnails and other data.
You mentioned that you have Plex installed on Drives 3 and 5. Are you talking about your Media or the actual Plex docker? Your media can be spanned like that, but I wouldn't encourage having your Plex docker spanned on two different disks like that. Could cause some issues.