Effects of single-point mutations on translocation of non-interacting heteropolymer protein chains

Abstract

AbstractWe analyse the role of single-point mutations on the translocation of heteropolymer protein chains with helical folding. We propose a statistical mechanics model that computes the equilibrium partition function of a given protein by incorporating experimental helix propensities of amino acids. From that we evaluate the free energy barrier for translocation and the average translocation time for single-point protein mutants and compared with wild-type proteins used as reference. In our calculations, single-point mutations that increase energy of the folded state in 5kJ/mol increase the energy barrier for translocation up to 50%, ∼0.75kBT, in consequence, the translocation time undergoes variations between 10% and 150% with the largest variations associated to substitutions of amino acids glycine and proline by alanine. In fact, substitutions of amino acids with the lowest helix propensities by amino acids with the largest helix propensities induced the largest mutational effects. These results indicate that effects of single-point mutations become evident when mutations increase energy of the folded state at least in ∼5kJ/mol. Our model predicts translocation time delays for proline to alanine single-point mutations which agree with deficiencies of protein translocation observed recently in experiments.Keywords: Statistical physicsfirst passage timepartition function AcknowledgmentsJosé Antonio Vélez-Pérez thanks Sistema Nacional de Investigadores (SNI) CONAHCyT for their support. Luis Olivares-Quiroz would like to acknowledge support from Sistema Nacional de Investigadores (SNI-CONAHCyT) and Colegio de Ciencia y Tecnología (CyT) Universidad Autónoma de la Ciudad de México UACM.Disclosure statementNo potential conflict of interest was reported by the author(s).