Saw a few other posts about this, some pretty negative and may have found some improvements.
Running SM 16.3.6642 on a Windows 2008R2 VM with 8GB of RAM. After initially running for about a day, the web interface got really slow. The server is running malware scanning and virus scanning at the OS and has 2 Spamassassin servers, Cyren Premium Antispam (trial), Clam and Cyren/F-Prot command-line scanning.
Initially the performance was pretty dismal, this article from 2013 (https://www.smartertools.com/blog/2013/05/16-improving-disk-io-and-overall-performance-for-your-mail-server-part-1) suggested limiting the resident shield, limiting where and what is scanned, disabling the pagefile, disable IIS logging for the Webmail interface and several other things.
In my case, I disabled the pagefile, disabled IIS logging for the SmarterMail IIS site and set the app pool to recycle daily at 1:00AM. For three days now the site has been running flawlessly (except for the nagging 'remember me' option (on or off) not allowing logins). I'm seeing immediate responses traversing throughout the entire web interface where before I was seeing 20-30 seconds after selecting any option. YMMV
Just wanted to post my experience and ask for any other suggestions you might have.