Analytical approaches to improve accuracy in solving the protein topology problem

Kamal Al Nasr, Feras Yousef, Ruba Jebril, Christopher Jones

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


To take advantage of recent advances in genomics and proteomics it is critical that the three-dimensional physical structure of biological macromolecules be determined. Cryo-Electron Microscopy (cryo-EM) is a promising and improving method for obtaining this data, however resolution is often not sufficient to directly determine the atomic scale structure. Despite this, information for secondary structure locations is detectable. De novo modeling is a computational approach to modeling these macromolecular structures based on cryo-EMderived data. During de novo modeling a mapping between detected secondary structures and the underlying amino acid sequence must be identified. DP-TOSS (Dynamic Programming for determining the Topology Of Secondary Structures) is one tool that attempts to automate the creation of this mapping. By treating the correspondence between the detected structures and the structures predicted from sequence data as a constraint graph problem DP-TOSS achieved good accuracy in its original iteration. In this paper, we propose modifications to the scoring methodology of DP-TOSS to improve its accuracy. Three scoring schemes were applied to DP-TOSS and tested: (i) a skeleton-based scoring function; (ii) a geometry-based analytical function; and (iii) a multi-well potential energy-based function. A test of 25 proteins shows that a combination of these schemes can improve the performance of DP-TOSS to solve the topology determination problem for macromolecule proteins.

Original languageEnglish (US)
Article number28
Issue number2
StatePublished - 2018
Externally publishedYes


  • Analysis
  • Cryo-electron microscopy
  • Geometry
  • Potential energy
  • Protein modeling
  • Protein secondary structure elements
  • Protein topology

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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