Sometimes it might happen that you run into very random issues and cannot reproduce the problem. This might happen due to the antivirus that is blocking temporary files to scan them and by this it's putting the files also in read only mode and this is most often the cause for some very strange behaviours in the Sharepoint/Project environment
Certain folders may have to be excluded from antivirus scanning when you use a file-level antivirus program in SharePoint
Also some great information regarding Antivirus software
• KB309422: Guidelines for choosing antivirus software to run on the computers that are running SQL Server http://support.microsoft.com/kb/309422?wa=wsignin1.0)• KB250355: Antivirus software that is not cluster-aware may cause problems with Cluster Services http://support.microsoft.com/kb/250355)
• KB943620: Folders to exclude when you perform a file-level antivirus scan on a server operating system http://support.microsoft.com/kb/943620• KB943556: Recommended file and folder exclusions for Microsoft Forefront Client Security or Forefront Endpoint Protection 2010 http://support.microsoft.com/kb/943556Regarding the question: Are the antivirus exclusions mandatory or not?
The exclusions are not mandatory there are a great number of variables involved in this answer, this is why, it is defined as a recommendation and could spare you from a lot of trouble.
Mark Russinovich’s Blog has an in depth article on the slow opening of Project Files: