Cα torsion angles as a flexible criterion to extract secrets from a molecular dynamics simulation

  • Fredrick Robin Devadoss Victor Paul Raj
  • Thomas E. ExnerEmail author
Original Paper
Part of the following topical collections:
  1. Topical Collection on the occasion of Prof. Tim Clark’s 65th birthday


Given the increasing complexity of simulated molecular systems, and the fact that simulation times have now reached milliseconds to seconds, immense amounts of data (in the gigabyte to terabyte range) are produced in current molecular dynamics simulations. Manual analysis of these data is a very time-consuming task, and important events that lead from one intermediate structure to another can become occluded in the noise resulting from random thermal fluctuations. To overcome these problems and facilitate a semi-automated data analysis, we introduce in this work a measure based on Cα torsion angles: torsion angles formed by four consecutive Cα atoms. This measure describes changes in the backbones of large systems on a residual length scale (i.e., a small number of residues at a time). Cluster analysis of individual Cα torsion angles and its fuzzification led to continuous time patches representing (meta)stable conformations and to the identification of events acting as transitions between these conformations. The importance of a change in torsion angle to structural integrity is assessed by comparing this change to the average fluctuations in the same torsion angle over the complete simulation. Using this novel measure in combination with other measures such as the root mean square deviation (RMSD) and time series of distance measures, we performed an in-depth analysis of a simulation of the open form of DNA polymerase I. The times at which major conformational changes occur and the most important parts of the molecule and their interrelations were pinpointed in this analysis. The simultaneous determination of the time points and localizations of major events is a significant advantage of the new bottom-up approach presented here, as compared to many other (top-down) approaches in which only the similarity of the complete structure is analyzed.


Visualization of the underlying idea of the new analysis method. Clustering of time series of Cα torsion angles are use to find events in molecular dynamics simulations. This was used to characterize the formation and scission events of a salt bridge in DNA polymerase I


Event detection C-alpha torsion angle Fuzzy clustering DNA polymerase I 



We thank Iris Adä and Michael Berthold for providing custom-made KNIME nodes and for helping in the design of the KNIME workflows. Fredrick Robin Devadoss V. acknowledges a stipend from the Konstanz Research School—Chemical Biology (KoRS-CB). The work was supported by the Zukunftskolleg and the Young Scholar Fund of the Universität Konstanz. Additionally, we thank the Common Ulm Stuttgart Server (CUSS) and the Baden-Württemberg grid (bwGRiD), which is part of the D-Grid system, for providing the computer resources that made the computations possible.

Supplementary material

894_2014_2196_MOESM1_ESM.docx (689 kb)
ESM 1 (DOCX 688 kb)
894_2014_2196_MOESM2_ESM.xls (17.1 mb)
ESM 2 (XLS 17511 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Fredrick Robin Devadoss Victor Paul Raj
    • 1
  • Thomas E. Exner
    • 1
    • 2
    Email author
  1. 1.Department of Chemistry, Konstanz Research School Chemical Biology, and ZukunftskollegUniversity of KonstanzKonstanzGermany
  2. 2.Theoretical Medicinal Chemistry and Biophysics, Institute of PharmacyEberhard Karls University TübingenTübingenGermany

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