diff --git a/domhmm/analysis/base.py b/domhmm/analysis/base.py
index c8e30e3..89ca137 100644
--- a/domhmm/analysis/base.py
+++ b/domhmm/analysis/base.py
@@ -269,6 +269,8 @@ def __init__(
         else:
             # User-specified trained HMM provided, check for consistency with expected format
 
+            assert not any(self.cluster_groups), "Chemical clustering is required, but pre-trained HMMs were provided. Chemical clustering does not require HMMs. Will terminate!"
+
             # Check for assymmetric membrane
             if self.asymmetric_membrane:
                 # Asymmetric membrane functionality was triggered! Assuming same/different lipid types per leaflet