MolCom: a method to compare protein molecules based on 3-D structural and chemical similarity.

This paper describes an improved method for conducting global feature comparisons of protein molecules in three dimensions and for producing a new form of multiple structure alignment. Our automated MolCom method incorporates an octtree strategy to partition and examine molecular properties in three-dimensional space at multiple levels of analysis. The MolCom method's multiple alignment is in the form of an octtree which locates regions in three-dimensional space where correspondence between molecules is identified based on a dynamic set of molecular features. MolCom offers a practical solution to the inherent compromise between computational complexity and analytical detail. MolCom is currently the only method that can analyze and compare a series of defined physicochemical properties using multiple, simultaneous levels of resolution. It is also the only method that provides a consensus structure outlining precisely where the similarity exists in three-dimensional space. Using a modest-sized collection of structural properties, separate experiments were conducted to calibrate MolCom and to verify that the spatial analyses and resulting structure alignments accurately identified both similar and dissimilar structures. The accuracy of MolCom was found to be over 99% and the similarity scores correlated strongly with the z-scores of the Alignment by Incremental Combinatorial Extension of the Optimal Path method.