Abstract
Prediction of the effect of amino acid substitutions on the thermodynamic stability of proteins is of great importance for studies into the molecular mechanisms underlying the abnormal function of mutant proteins, interpretation of genotyping results, and purposeful design of modified proteins with improved biomedical and biotechnological properties. A set of methods was developed for predicting the changes in free energy (ΔΔG) of mutant proteins containing single substitutions using the information only about protein primary structure or also about the spatial structure. A modified KRAB algorithm was used; its higher accuracy in predicting the changes in the thermodynamic stability of mutant proteins compared with the other known methods designed for solving this problem is demonstrated. Distribution of the positions in the sequence of Malayan pit viper venom protein (kistrin) where the substitutions decrease or increase kistrin stability is analyzed. The substitutions at most positions conserved in the disintegrin family decrease the stability of this protein, except for several positions whose conservation can be determined by functional significance.
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A. Friedler, D. B. Veprintsev, L. O. Hansson, and A. R. Fersht, J. Biol. Chem. 278(26), 24108 (2003).
I. N. Gorshkova, T. Liu, V. I. Zannis, and D. Atkinson, Biochemistry 41(33), 10529 (2002).
M. Lehmann and M. Wyss, Curr. Opin. Biotechnol. 12(4), 371 (2001).
L. X. Dang, K. M. Merz, and P. A. Kollman, J. Am. Chem. Soc. 111, 8505 (1989).
M. Prevost, S. J. Wodak, B. Tidor, and M. Karplus, Proc. Natl. Acad. Sci. USA 88, 10880 (1991).
J. W. Pitera and P. A. Kollman, Proteins 41, 385 (2000).
D. Gilis and M. Rooman, J. Mol. Biol. 272, 276 (1997)
C. M. Topham, N. Srinivasan, and T. L. Blundell, Prot. Eng. 101, 46 (1997).
D. Gilis and M. Rooman, Theor. Chem. Acc. 101, 46 (1999).
E. Capriotti, P. Fariselli, and R. Casadio, Bioinformatics 20(Suppl. 1), i63 (2004).
E. Capriotti, P. Fariselli, R. Calabrese, and R. Casadio, Bioinformatics 21(Suppl. 2), ii54 (2005).
K. A. Bava, M. M. Gromiha, H. Uedaira, et al., Nucleic Acids Res. 32, 120 (2004).
A. Bairoch and R. Apweiler, Nucleic Acids Res. 24(1), 21 (1996).
H. M. Berman, J. Westbrook, Z. Feng, et al., Nucleic Acids Res. 28(1), 235 (2000).
M. M. Gromiha, J. An, H. Kono, et al., Nucleic Acids Res. 28(1), 283 (2000).
R. Guerois, J. E. Nielsen, and L. Serrano, J. Mol. Biol. 320(2), 369 (2002).
D. Frishman and P. Argos, Proteins 23(4), 566 (1995).
N. G. Zagoruiko, Applied Methods for Analysis of Data and Knowledge (Institut Matematiki, Novosibirsk, 1999) [in Russian].
R. K. Prim, in Cybernetics Transactions (Nauka, Moscow, 1961), no. 2, pp. 95–107.
E. Capriotti, P. Fariselli, and R. Casadio, Nucleic Acids Res. 33 (Web Server issue), W306 (2005).
J. Cheng, A. Randall, and P. Baldi, Proteins 62(4), 1125 (2006).
M. S. Dennis, P. Carter, and R. A. Lazarus, Proteins 15(3), 312 (1993).
D. A. Afonnikov and N. A. Kolchanov, Nucleic Acids Res. 32, W64 (2004).
D. A. Afonnikov, D. Yu. Oshchepkov, and N. A. Kolchanov, Bioinformatics 17, 1035 (2001).
K. H. Park, K. Na, and H. M. Chung, Biotechnol. Lett. 27(4), 227 (2005).
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Demenkov, P.S., Aman, E.E. & Ivanisenko, V.A. Prediction of the changes in thermodynamic stability of proteins caused by single amino acid substitutions. BIOPHYSICS 51 (Suppl 1), 49–53 (2006). https://doi.org/10.1134/S0006350906070104
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DOI: https://doi.org/10.1134/S0006350906070104