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. Author manuscript; available in PMC: 2023 Sep 15.
Published in final edited form as: J Phys Chem B. 2022 Aug 30;126(36):6780–6791. doi: 10.1021/acs.jpcb.2c03806

Table 1.

Timeline of methods for Hsp70 binding site prediction and their key insights. The acronym PSSM stands for Position-specific Scoring Matrix. They are 20 by N matrices (20 amino acids, N substrate residues) and are often given in energy units, so that each element in the matrix is the binding affinity per amino acid and substrate position.

Model or Authors Year Chaperone Key features and insights Online tool/code Citation
Blond-Elguindi et al. 1993 BiP PSSM based on sequence statistics -- 42,65
Gragerov et al.; Ivey et al. 1994 DnaK Binding analysis from random peptide phage display. -- 43,44
Rüdiger et al. 1997 DnaK Identification of the canonical binding motif -- 45
Rüdiger et al.; Srinivasan et al. 2001; 2012 DnaJ DnaJ and DnaK share many targets -- 46,66
LIMBO 2009 DnaK FoldX 49 and Structure-based PSSM improves transferability of sequence-based PSSM https://limbo.switchlab.org/ 55
BiPPred 2016 BiP MD-based PSSM requires minimal training and no sequence-based PSSM https://www.bioinformatics.wzw.tum.de/bippred/submit/ 60
ChaperISM 2019 DnaK Position-Independent Scoring Matrix (PISM) improves agreement with binding array data https://github.com/BioinfLab/ChaperISM 56
Paladin 2021 DnaK MD-based PSSM, substrate register and orientation prediction https://github.com/enordquist/paladin 41