TY - JOUR

T1 - Multi-Gaussian Monte Carlo Analysis of PELDOR Data in the Frequency Domain

AU - Matveeva, Anna G.

AU - Yushkova, Yulia V.

AU - Morozov, Sergei V.

AU - Grygor'Ev, Igor A.

AU - Dzuba, Sergei A.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Pulsed double electron-electron resonance technique (PELDOR or DEER) is often applied to study conformations and aggregation of spin-labelled macromolecules. Because of the ill-posed nature of the integral equation determining the distance distribution function, a regularization procedure is required to restrict the smoothness of the solution. In this work, we performed PELDOR measurements for new flexible nitroxide biradicals based on trolox, which is the synthetic analogue of α-tocopherol; spin-labelled trolox derivatives are investigated as potential anti-cancer drugs. We use regularization by an approximation of the solution with a sum of limited number of Gaussians, by varying their positions, widths and amplitudes. Their best-fitted values were found by a completely random Monte Carlo process. The use of the frequency-domain PELDOR data allowed diminution of the artifacts induced by spin-spin electron-nuclear and intermolecular electron-electron interactions. It was found that for the all biradicals studied, the use of three Gaussians was enough for good agreement with the experiments. The number of trials for obtaining satisfactory result was found to be quite reasonable, which is explained by presence of the singularity in the core of integral equation. The maxima of inter-spin distance distribution for different biradicals were found to vary between 1.5 and 2.3 nm, depending on the linkers between the Trolox core and nitroxides. The distance distributions around these positions reflect flexibility of the biradicals.

AB - Pulsed double electron-electron resonance technique (PELDOR or DEER) is often applied to study conformations and aggregation of spin-labelled macromolecules. Because of the ill-posed nature of the integral equation determining the distance distribution function, a regularization procedure is required to restrict the smoothness of the solution. In this work, we performed PELDOR measurements for new flexible nitroxide biradicals based on trolox, which is the synthetic analogue of α-tocopherol; spin-labelled trolox derivatives are investigated as potential anti-cancer drugs. We use regularization by an approximation of the solution with a sum of limited number of Gaussians, by varying their positions, widths and amplitudes. Their best-fitted values were found by a completely random Monte Carlo process. The use of the frequency-domain PELDOR data allowed diminution of the artifacts induced by spin-spin electron-nuclear and intermolecular electron-electron interactions. It was found that for the all biradicals studied, the use of three Gaussians was enough for good agreement with the experiments. The number of trials for obtaining satisfactory result was found to be quite reasonable, which is explained by presence of the singularity in the core of integral equation. The maxima of inter-spin distance distribution for different biradicals were found to vary between 1.5 and 2.3 nm, depending on the linkers between the Trolox core and nitroxides. The distance distributions around these positions reflect flexibility of the biradicals.

KW - Biradicals

KW - DEER

KW - DNA

KW - Fredholm equation regularization

KW - Monte Carlo fitting

KW - peptide antibiotics

KW - RNA

KW - spin labels

KW - Trolox

KW - biradicals

KW - ELDOR

KW - DISTANCE MEASUREMENTS

KW - DISTRIBUTIONS

KW - PEPTIDES

KW - TRICHOGIN GA-IV

KW - BIOMACROMOLECULES

KW - ELECTRON DOUBLE-RESONANCE

KW - SPIN LABELS

KW - EPR SPECTROSCOPY

UR - http://www.scopus.com/inward/record.url?scp=85012285843&partnerID=8YFLogxK

U2 - 10.1515/zpch-2016-0830

DO - 10.1515/zpch-2016-0830

M3 - Article

AN - SCOPUS:85012285843

VL - 231

SP - 671

EP - 688

JO - Zeitschrift fur Physikalische Chemie

JF - Zeitschrift fur Physikalische Chemie

SN - 0942-9352

IS - 3

ER -