1.) Disable the SM web server:

Click Start -> Programs -> SmarterTools -> SmarterMail -> Configure SmarterMail Web Server
Click the Stop button. Change the Startup Mode to Disabled. Click the Apply button. Click the Close button.

2.) Add IIS ISAPI Components:

Open up IIS. Launch IIS Manager. Click on Products tab. Click Servers.
Install required components of: IIS: ASP.NET, .NET Extensibility, ASP, CGI, ISAPI Extensions, ISAPI Filters. Click Install.

3.) Add an Application Pool:

Open IIS Manager. Right click on Application Pools and choose Add Application Pool. Name the new application pool SmarterMail, or something easy to identify. Set the .Net Framework Version to v4.0.x. Set the Application Pools Managed Pipeline to 'Integrated'. Make sure "Start application pool immediately" is checked. Click OK.

4.) Add SmarterMail to IIS:

Open IIS Manager. Click on your Server Name, and on the right side, under IIS, double-click ISAPI and CGI Restrictions. Verify that ASP.NET v4.0 is allowed (If not, right click on ASP.NET v4.0.x and select Allowed). On the left side of the page, right click on Sites and choose Add Website. Name the site SmarterMail. If you created an Application Pool name other than SmarterMail, click Select and choose the correct Application Pool. For the physical path, browse to the SmarterMail -> MRS folder. The default location is C:\Program Files (x86)\SmarterTools\SmarterMail\MRS. For Binding, choose an IP address to use for Webmail. If this IP address is shared with another Web site, you will need to use a different port or Host Headers. Make sure "Start Web site immediately" is checked. Click OK

5.) Verify IIS Settings:

In IIS Manager, click on your ServerName. Under IIS, double click ISAPI and CGI Restrictions.
Verify that ASP .NET v4.0 is allowed. If it is not, right-click on ASP .NET v4.0 and select Allowed.
In the tree view, click Sites. Expand the SmarterMail site. Click on the App_Themes folder. Under IIS, double click HTTP Response Headers. Under the Action menus, click Set Common Headers. Enable the Expire Web content setting. Click After. Add 7. Click OK. Click on Application Pools in the tree view. Right click on the SmarterMail app pool. Select Advanced Settings. Under the Process Model heading, ensure the Identity is set to NetworkService. From the Windows Services area of your server, verify that the World Wide Publishing Service is running.