diff --git a/pkgs/applications/science/chemistry/pymol/default.nix b/pkgs/applications/science/chemistry/pymol/default.nix
index fcae70149392..b0f6adf1f933 100644
--- a/pkgs/applications/science/chemistry/pymol/default.nix
+++ b/pkgs/applications/science/chemistry/pymol/default.nix
@@ -39,6 +39,8 @@ in
 python3Packages.buildPythonApplication rec {
   inherit pname;
   version = "3.0.0";
+  pyproject = true;
+
   src = fetchFromGitHub {
     owner = "schrodinger";
     repo = "pymol-open-source";
@@ -46,22 +48,27 @@ python3Packages.buildPythonApplication rec {
     hash = "sha256-GhTHxacjGN7XklZ6gileBMRZAGq4Pp4JknNL+qGqrVE=";
   };
 
+  postPatch = ''
+    substituteInPlace setup.py \
+      --replace-fail "self.install_libbase" '"${placeholder "out"}/${python3.sitePackages}"'
+  '';
+
+  build-system = [
+    python3Packages.setuptools
+  ];
+
   nativeBuildInputs = [ qt5.wrapQtAppsHook ];
   buildInputs = [ python3Packages.numpy python3Packages.pyqt5 glew glm libpng libxml2 freetype msgpack netcdf ];
   env.NIX_CFLAGS_COMPILE = "-I ${libxml2.dev}/include/libxml2";
   hardeningDisable = [ "format" ];
 
-  installPhase = ''
-    python setup.py install --home="$out"
-    runHook postInstall
-  '';
-
   postInstall = with python3Packages; ''
     wrapProgram $out/bin/pymol \
       --prefix PYTHONPATH : ${lib.makeSearchPathOutput "lib" python3.sitePackages [ pyqt5 pyqt5.pyqt5-sip ]}
 
     mkdir -p "$out/share/icons/"
-    ln -s ../../lib/python/pymol/pymol_path/data/pymol/icons/icon2.svg "$out/share/icons/pymol.svg"
+    ln -s $out/${python3.sitePackages}/pymol/pymol_path/data/pymol/icons/icon2.svg "$out/share/icons/pymol.svg"
+  '' + lib.optionalString stdenv.hostPlatform.isLinux ''
     cp -r "${desktopItem}/share/applications/" "$out/share/"
   '';