Proton (Steam Play 2.0) is a set of game-focused patches on top of Wine, plus several other components that improve game compatibility and/or performance. The most notable of these are DXVK, which implements Direct3D 8/9/10/11 APIs in terms of Vulkan, and vkd3d-proton, which does the same for Direct3D 12.
In many cases, it's possible to get a game running with regular Wine (or Wine-staging) if you install into the Wine prefix not only the game, but also one or more of: DXVK, vkd3d-proton, whatever Microsoft Visual C++ runtime the game wants, and Mono. If a game also needs custom Wine patches, you'll have better luck with a game manager like Lutris, which automates installing patched Wine versions, or running a Wine build like the one that GloriousEggroll maintained until recently.
Be sure that your graphics card's Vulkan drivers are installed, and if it's a 32-bit game, all the appropriate 32-bit libraries as well.
Valve's issue tracker for games running in Proton often has comments that are helpful when trying to bring up a game in Wine.
In many cases, it's possible to get a game running with regular Wine (or Wine-staging) if you install into the Wine prefix not only the game, but also one or more of: DXVK, vkd3d-proton, whatever Microsoft Visual C++ runtime the game wants, and Mono. If a game also needs custom Wine patches, you'll have better luck with a game manager like Lutris, which automates installing patched Wine versions, or running a Wine build like the one that GloriousEggroll maintained until recently.
Be sure that your graphics card's Vulkan drivers are installed, and if it's a 32-bit game, all the appropriate 32-bit libraries as well.
Valve's issue tracker for games running in Proton often has comments that are helpful when trying to bring up a game in Wine.
https://github.com/ValveSoftware/Proton
https://github.com/doitsujin/dxvk
https://github.com/HansKristian-Work/vkd3d-proton
https://github.com/GloriousEggroll/wine-ge-custom
https://github.com/ValveSoftware/Proton/issues