pFolMech
Protein Biophysics Lab
Predicting Folding Free Energy Profiles, Conformational Landscapes, and Folding Mechanisms
1. Naganathan, A. N., Dani, R., Gopi, S., Aranganathan, A., & Narayan, A. (2021). Folding Intermediates, Heterogeneous Native Ensembles and Protein Function. J. Mol. Biol., 167325. 
2. Soundhararajan Gopi, Akashnathan Aranganathan & Athi N. Naganathan (2019). Thermodynamics and Folding Landscapes of Large Proteins from a Statistical Mechanical Model. Curr. Res. Struct. Biol., 1, 6-12.
Also, please cite the literature source associated with the modules you have used.
- STRIDE: Heinig, M., & Frishman, D. STRIDE: a Web server for secondary structure assignment from known atomic coordinates of proteins. Nucl. Acids Res., 2004, 32, W500-2.
- WHAT IF: Rodriguez, R., Chinea, G., Lopez, N., Pons, T., & Vriend, G. Homology modeling, model and software evaluation: three related resources. CABIOS, 1998, 14, 523-528.
399 PDB files were analyzed using this web-server, since July 4, 2021.
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pFolMech Overview
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The pFolMech web-server predicts the folding free energy profile and conformational landscape of a protein employing the structure-based statistical mechanical WSME (Wako-Saitô-Muñoz-Eaton) model (Wako H & Saitô N, 1978; Muñoz V & Eaton WA, 1999; Naganathan AN, 2012; Gopi et al., 2019) with just the protein structure as an input. The version of the model employed here uses sequence approximations - SSA (single sequence approximation), DSA (double sequence approximation) and DSAw/L (double sequence approximation allowing for interaction between folded islands) microstates - to construct an ensemble of states whose relative populations are determined by the strength of van der Waals interactions, Debye-Hückel electrostatics, and simplified solvation free energy derived from the PDB structure apart from structure-sequence based residue-level conformational entropy terms. To account for a large number of microstates, the server employs a recently developed block approximation that treats a block of consecutive residues as the fundamental folding unit for large proteins. The block sizes are defined as proportional to the size of the proteins with a maximum block size of 5 for a protein comprising of 500 amino acids.
We expect this server to provide insights into protein folding mechanisms while facilitating the identification of likely partially-structured conformations accessed by the protein in its native ensemble, relative barrier heights, and the number and nature of folding intermediates. In this web-server version, the model parameters are not calibrated against experimental data and hence the predictions are qualitative. Care should also be taken to ensure that the input structure is not missing any atoms.
The results from the queued/completed jobs are being temporarily stored by the server and can be retrieved within five days from the date of job completion. The job results will not be available through the link(s) / job-ID provided to you after this time span.
2022, Maintained by Protein Biophysics Lab, IIT Madras, Chennai-36, India
Last Updated: February 8, 2022