The threading or "remote homology design" is a 3D structure prediction technique used when twilight zone is reached (meaning less than 25% of identity between 2 proteins in a pair-wise alignment). In this case the homology modeling approach is unreliable. The process takes the target sequence and evaluates its fitting against different known folds. The concept of "fitting" varies within threading programs. It can be for instance secondary structure coincidence, similar or not accesibility on solvatation energy, etc.

            In general, methods of protein fold recognition attempt to detect similarities in 3D features in proteins showing no sequence similarity. Basically the main goal of these methods is to find folds that might be compatible with a sequence. Unlike sequence-only methods, threading methods are capable to obtain additional information from 3D data. Therefore: rather than prediciting how a sequence folds, these methods predict how well a fold might fit a sequence.