MultiBind: Multiple Alignment of Protein Binding Sites


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Multiple Alignment of Protein Binding Sites Recognizes Spatial Chemical Binding Patterns Common to a Set of Protein Structures

Abstract:

MultiBind is a novel computational method, for recognition of binding patterns common to a set of protein structures. It performs a multiple alignment between protein binding sites in the absence of overall sequence, fold or binding partner similarity. MultiBind recognizes common spatial arrangements of physico-chemical properties in the binding sites. These should be important for recognition of function, prediction of binding and drug design.

The MultiBind method, applies an efficient Geometric Hashing technique to detect a potential set of multiple alignments of the given binding sites. To overcome the exponential number of possible multiple combinations it applies a very efficient filtering procedure which is heavily based on the selected scoring function. Our method guarantees detection of an approximate solution in terms of pattern proximity as well as cardinality of multiple alignment.

Biological Motivation:

There are numerous examples of proteins that have totally different overall sequences and folds, but bind similar binding partners. The most common examples are proteins that bind such molecules as ATP/ANP, estradiol and other small molecules.

Question:

The question that MultiBind helps to address is why does it happen? Why can different protein molecules (potentially with no common sequence or backbone patterns) bind similar binding partners?

Hypothesis:

Protein binding sites which bind similar ligand and perfrom similar function share a certain 3D physico-chemical pattern. MultiBind aligns between a set of protein binding sites and recognizes the common spatial arrangement of physico-chemical properties ("receptor based pharmacophore").