As already stated, an assembly signature is invalidated when instrumenting (or otherwise modifying) a signed assembly.
The irony is that instrumentation is not required to do profiling/coverage analysis as .NET has an API for this. For some obscure reason, however, the Visual Studio coverage analysis and profiler does not use this API...
Third party products such as the profilers dotTrace and ANTS, or coverage analysis tools such as NCover, use the API approach and thus have no need to tamper with the assemblies themselves.
In our current project, exactly this problem made us purchase 3rd party tooling since developing without signing in our very complex solution would take a massive effort due to a lot of reflection and was out of the question.