Journal of Computer-Aided Molecular Design

, Volume 33, Issue 2, pp 265–285 | Cite as

Structural characterization and molecular dynamics simulations of the caprine and bovine solute carrier family 11 A1 (SLC11A1)

  • Kostas A. TriantaphyllopoulosEmail author
  • Fotis A. Baltoumas
  • Stavros J. Hamodrakas


Natural Resistance-Associated Macrophage Proteins are a family of transmembrane divalent metal ion transporters, with important implications in life of both bacteria and mammals. Among them, the Solute Carrier family 11 member A1 (SLC11A1) has been implicated with susceptibility to infection by Mycobacterium avium subspecies paratuberculosis (MAP), potentially causing Crohn’s disease in humans and paratuberculosis (PTB) in ruminants. Our previous research had focused on sequencing the mRNA of the caprine slc11a1 gene and pinpointed polymorphisms that contribute to caprine SLC11A1’s susceptibility to infection by MAP in PTB. Despite its importance, little is known on the structural/dynamic features of mammalian SLC11A1 that may influence its function under normal or pathological conditions at the protein level. In this work we studied the structural architecture of SLC11A1 in Capra hircus and Bos taurus through molecular modeling, molecular dynamics simulations in different, functionally relevant configurations, free energy calculations of protein-metal interactions and sequence conservation analysis. The results of this study propose a three dimensional structure for SLC11A1 with conserved sequence and structural features and provide hints for a potential mechanism through which divalent metal ion transport is conducted. Given the importance of SLC11A1 in susceptibility to PTB, this study provides a framework for further studies on the structure and dynamics of SLC11A1 in other organisms, to gain 3D structural insight into the macromolecular arrangements of SLC11A1 but also suggesting a potential mechanism which divalent metal ion transport is conducted.


SLC11A1 NRAMP Paratuberculosis Ion transport Molecular dynamics Energy calculations 



Solute carrier family 11 member 1 gene


Solute carrier family 11 member A1


Natural resistance-associated macrophage proteins


Divalent metal ion transporer 1


Mycobacterium avium subspecies paratuberculosis


Staphylococcus capitis divalent metal ion transporter


Eremococcus coleocola divalent metal ion transporter


Deinococcus radiodurans NRAMP homolog




Molecular dynamics


Free energy perturbation


Essential dynamics analysis



We thank the authors from both the Agricultural University of Athens and the National and Kapodistrian University of Athens for the conception, enthusiasm and continuous support of the work. We would also like to thank the anonymous reviewers for their comments and the associate editor for their proper handling of the manuscript. This work was supported by computational time granted from the Greek Research & Technology Network (GRNET) in the National HPC facility—ARIS under project IDs “PR002041-S.C.S.M.P.” and “PR004006-BioMemPro-MD”.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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Supplementary material 1 (PDF 8960 KB)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Kostas A. Triantaphyllopoulos
    • 1
    Email author
  • Fotis A. Baltoumas
    • 2
  • Stavros J. Hamodrakas
    • 2
  1. 1.Department of Animal Breeding and Husbandry, Faculty of Animal Science and Aquaculture, School of Agricultural Production, Infrastructure and EnvironmentAgricultural University of AthensAthensGreece
  2. 2.Section of Cell Biology and Biophysics, Department of Biology, School of SciencesNational and Kapodistrian University of AthensAthensGreece

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