LPTD: A novel linear programming-based topology determination method for cryo-EM maps

Bahareh Behkamal, Mahmoud Naghibzadeh, Andrea Pagnani, Mohammad Reza Saberi, Kamal Al Nasr

Research output: Contribution to journalArticlepeer-review


Topology determination is one of the most important intermediate steps toward building the atomic structure of proteins from their medium-resolution cryo-electron microscopy (cryo-EM) map. The main goal in the topology determination is to identify correct matches (i.e. assignment and direction) between secondary structure elements (SSEs) (α-helices and β-sheets) detected in a protein sequence and cryo-EM density map. Despite many recent advances in molecular biology technologies, the problem remains a challenging issue. To overcome the problem, this article proposes a linear programming-based topology determination (LPTD) method to solve the secondary structure topology problem in three-dimensional geometrical space. Through modeling of the protein's sequence with the aid of extracting highly reliable features and a distance-based scoring function, the secondary structure matching problem is transformed into a complete weighted bipartite graph matching problem. Subsequently, an algorithm based on linear programming is developed as a decision-making strategy to extract the true topology (native topology) between all possible topologies. The proposed automatic framework is verified using 12 experimental and 15 simulated α-β proteins. Results demonstrate that LPTD is highly efficient and extremely fast in such a way that for 77% of cases in the dataset, the native topology has been detected in the first rank topology in <2 s. Besides, this method is able to successfully handle large complex proteins with as many as 65 SSEs. Such a large number of SSEs have never been solved with current tools/methods.

Original languageEnglish (US)
Pages (from-to)2734-2741
Number of pages8
Issue number10
StatePublished - May 15 2022
Externally publishedYes

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics


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