About CABS-flex 2.0

CABS-flex is an efficient modeling procedure for fast simulations of protein structure flexibility [1]. It is based on the CABS model, a well-established coarse-grained protein modeling tool – CABS design and applications have been recently reviewed in [2]. The CABS model may generate protein dynamics at highly reduced (3 orders of magnitude) computational cost, although with some decrease in resolution. The CABS-flex server – version 1.0 has been introduced in 2013 [3] – follows the work of Jamroz et al. [4], where the authors demonstrated, that the consensus view of protein near-native dynamics obtained from 10-nanosecond MD simulations (all-atom, explicit water, for all protein metafolds using the four most popular force-fields), is consistent with the CABS dynamics. It has been also demonstrated that fluctuations of protein residues obtained from CABS-flex are well correlated to those of NMR ensembles [5]. CABS-flex method is also used as a part of the AGGRESCAN3D method for the prediction of protein aggregation propensity [6] (AGGRESCAN3D employs CABS-flex to take into account the influence of the dynamic protein structure fluctuations on the aggregation propensity). Moreover, CABS-flex methodology is a component of the CABS-dock method for protein-peptide docking [7-9] , which allows for significant flexibility of the peptide and the protein receptor during explicit simulation of peptide binding.

The only data required as input is a protein structure in the PDB format (or a protein PDB code). The input structure is used as a starting point for the CABS simulation. The resulting trajectory is automatically analyzed and processed to provide the useful description of protein dynamics (see Figure 1).


An important attribute of protein models generated by the CABS is that their spatial resolution (in C-alpha chain format) allows for reconstruction of all-atom representation of physically realistic models. The output set of all-atom models is generated through trajectory clustering (by k-medoids method) and subsequent multi-step reconstruction and optimization procedures (using Modeller package [9]

CABS-flex 2.0 version has been based on newly developed CABS-flex standalone package, available at https://bitbucket.org/lcbio/cabsflex, which offer a multitude of additional modeling options.

References

  1. Kuriata, A.*, Gierut, A.M.*, Oleniecki, T., Ciemny, M.P., Kolinski, A., Kurcinski, M., Kmiecik, S. (2018), CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures. Nucleic acids research.
  2. Kmiecik, S., Gront, D., Kolinski, M., Wieteska, L., Dawid, A.E. and Kolinski, A. (2016), Coarse-Grained Protein Models and Their Applications. Chemical reviews, 116, 7898-7936.
  3. Jamroz, M., Kolinski, A. and Kmiecik, S. (2013), CABS-flex: Server for fast simulation of protein structure fluctuations. Nucleic acids research, 41, W427-431.
  4. Jamroz, M., Orozco, M., Kolinski, A. and Kmiecik, S. (2013), Consistent View of Protein Fluctuations from All-Atom Molecular Dynamics and Coarse-Grained Dynamics with Knowledge-Based Force-Field. Journal of chemical theory and computation, 9, 119-125.
  5. Jamroz, M., Kolinski, A. and Kmiecik, S. (2014), CABS-flex predictions of protein flexibility compared with NMR ensembles. Bioinformatics, 30, 2150-2154.
  6. Zambrano, R., Jamroz, M., Szczasiuk, A., Pujols, J., Kmiecik, S. and Ventura, S. (2015), AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures. Nucleic Acids Res, 43, W306-313.
  7. Kurcinski, M., Jamroz, M., Blaszczyk, M., Kolinski, A. and Kmiecik, S. (2015), CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site. Nucleic acids research, 43, W419-424.
  8. Blaszczyk, M., Kurcinski, M., Kouza, M., Wieteska, L., Debinski, A., Kolinski, A. and Kmiecik, S. (2016), Modeling of protein-peptide interactions using the CABS-dock web server for binding site search and flexible docking. Methods, 93, 72-83.
  9. Ciemny, M.P., Debinski, A., Paczkowska, M., Kolinski, A., Kurcinski, M. and Kmiecik, S. (2016), Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. Sci Rep, 6, 37532.
  10. Webb, B. and Sali, A. (2017), Protein Structure Modeling with MODELLER. Methods Mol Biol, 1654, 39-54.