RANKING VALID TOPOLOGIES OF THE SECONDARY STRUCTURE ELEMENTS USING A CONSTRAINT GRAPH

KAMAL AL NASR, DESH RANJAN, MOHAMMAD ZUBAIR, JING HE
2011 Journal of Bioinformatics and Computational Biology  
Electron cryo-microscopy is a fast advancing biophysical technique to derive threedimensional structures of large protein complexes. Using this technique, many density maps have been generated at intermediate resolution such as 6-10Å resolution. Although it is challenging to derive the backbone of the protein directly from such density maps, secondary structure elements such as helices and β-sheets can be computationally detected. Our work in this paper provides an approach to enumerate the
more » ... ranked possible topologies instead of enumerating the entire population of the topologies. This approach is particularly practical for large proteins. We developed a directed weighted graph, the topology graph, to represent the secondary structure assignment problem. We prove that the problem of finding the valid topology with the minimum cost is NP hard. We developed an O(N 2 2 N ) dynamic programming algorithm to identify the topology with the minimum cost. The test of 15 proteins suggests that our dynamic programming approach is feasible to work with proteins of much larger size than we could before. The largest protein in the test contains 18 helical sticks detected from the density map out of 33 helices in the protein.
doi:10.1142/s0219720011005604 pmid:21714133 fatcat:y4rzdxqcqbhzpcy42wes6n7umq