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Effective approach for calculations of absolute stability of proteins using focused dielectric constants
Author(s) -
Vicatos Spyridon,
Roca Maite,
Warshel Arieh
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22481
Subject(s) - dipole , dielectric , protein stability , stability (learning theory) , chemistry , work (physics) , electrostatics , charge (physics) , mean absolute error , computational chemistry , thermodynamics , physics , statistical physics , mathematics , mean squared error , computer science , quantum mechanics , statistics , machine learning , organic chemistry , biochemistry
The ability to predict the absolute stability of proteins based on their corresponding sequence and structure is a problem of great fundamental and practical importance. In this work, we report an extensive, refinement and validation of our recent approach (Roca et al ., FEBS Lett 2007;581:2065–2071) for predicting absolute values of protein stability Δ G fold . This approach employs the semimacroscopic protein dipole Langevin dipole method in its linear response approximation version (PDLD/S‐LRA) while using the best fitted values of the dielectric constants ε′ p and ε′ eff for the self energy and charge–charge interactions, respectively. The method is validated on a diverse set of 45 proteins. It is found that the best fitted values of both dielectric constants are around 40. However, the self energy of internal residues and the charge–charge interactions of Lys have to be treated with care, using a somewhat lower values of ε′ p and ε′ eff . The predictions of Δ G fold reported here, have an average error of only 1.8 kcal/mole compared to the observed values, making our method very promising for estimating protein stability. It also provides valuable insight into the complex electrostatic phenomena taking place in folded proteins. Proteins 2009. © 2009 Wiley‐Liss, Inc.