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

This paper describes an improved method for conducting globalfeature comparisons of protein molecules in three dimensionsand for producing a new form of multiple structure alignment.Our automated MolCom method incorporates an octtree strategyto partition and examine molecular properties in three-dimensionalspace at multiple levels of analysis. The MolCom method’smultiple alignment is in the form of an octtree which locatesregions in three-dimensional space where correspondence betweenmolecules is identified based on a dynamic set of molecularfeatures. MolCom offers a practical solution to the inherentcompromise between computational complexity and analytical detail.MolCom is currently the only method that can analyze and comparea series of defined physicochemical properties using multiple,simultaneous levels of resolution. It is also the only methodthat provides a consensus structure outlining precisely wherethe similarity exists in three-dimensional space. Using a modest-sizedcollection of structural properties, separate experiments wereconducted to calibrate MolCom and to verify that the spatialanalyses and resulting structure alignments accurately identifiedboth similar and dissimilar structures. The accuracy of MolComwas found to be over 99% and the similarity scores correlatedstrongly with the z-scores of the Alignment by Incremental CombinatorialExtension of the Optimal Path method.