Hydration of a B-DNA Fragment in the Method of Atom-atom Correlation Functions with the Reference Interaction Site Model Approximation

We propose an efficient numerical algorithm for solving integral equations of the theory of liquids in the Reference Interaction Site Model (RISM) approximation for infinitely dilute solution of macromolecules with a large number of atoms. The algorithm is based on applying the nonstationary iterative methods for solving systems of linear algebraic equations. We calculate the solvent-solute atom-atom correlation functions for a fragment of the B-DNA duplex d(GGGGG).d(CCCCC) in infinitely dilute aqueous solution. The obtained results are compared with available experimental data and results from computer simulations.Comment: 9 pages, RevTeX, 9 pages of ps figures, accepted for publications in JC

ОПЫТ ПРИМЕНЕНИЯ НОВЫХ РЕЖИМОВ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА С МНОЖЕСТВЕННОЙ И ШИРОКОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ В РЕСПУБЛИКЕ БЕЛАРУСЬ

The objective of the study: to describe the efficiency and safety of new anti-tuberculosis drugs when treating tuberculosis patients with drug resistance.Subjects and methods. In Belarus, the retrospective and prospective analyses were performed in the cohort of 300 patients with multiple drug resistance and high rates of extensive drug resistance, who were treated with new drugs and drugs which were started to be used for the treatment of tuberculosis. In order to describe the cohort, blocks of variables were used to specify the efficiency and safety profiles of new anti-tuberculosis drugs.Results of the study. The high level of therapeutic efficiency of new regimens and their fairly favorable safety profile were demonstrated in the cohort.Цель исследования: характеристика профиля эффективности и безопасности использования новых противотуберкулезных лекарственных средств у пациентов с туберкулезом с лекарственной устойчивостью возбудителя.Материалы и методы. Проведен ретроспективный и проспективный анализ когорты из 300 пациентов с туберкулезом с множественной лекарственной устойчивостью возбудителя и высокой долей широкой лекарственной устойчивости, получавших новые и перепрофилированные противотуберкулезные лекарственные средства, в Республике Беларусь. Для описания когорты использовали группы переменных для характеристики профиля эффективности и профиля безопасности новых противотуберкулезных лекарственных средств.Результаты исследования. Продемонстрирован высокий уровень терапевтической эффективности в исследованной когорте, а также достаточно благоприятный профиль безопасности новых режимов

BayesPI - a new model to study protein-DNA interactions: a case study of condition-specific protein binding parameters for Yeast transcription factors

<p>Abstract</p> <p>Background</p> <p>We have incorporated Bayesian model regularization with biophysical modeling of protein-DNA interactions, and of genome-wide nucleosome positioning to study protein-DNA interactions, using a high-throughput dataset. The newly developed method (BayesPI) includes the estimation of a transcription factor (TF) binding energy matrices, the computation of binding affinity of a TF target site and the corresponding chemical potential.</p> <p>Results</p> <p>The method was successfully tested on synthetic ChIP-chip datasets, real yeast ChIP-chip experiments. Subsequently, it was used to estimate condition-specific and species-specific protein-DNA interaction for several yeast TFs.</p> <p>Conclusion</p> <p>The results revealed that the modification of the protein binding parameters and the variation of the individual nucleotide affinity in either recognition or flanking sequences occurred under different stresses and in different species. The findings suggest that such modifications may be adaptive and play roles in the formation of the environment-specific binding patterns of yeast TFs and in the divergence of TF binding sites across the related yeast species.</p

Assessment of hardening due to dislocation loops in bcc iron: Overview and analysis of atomistic simulations for edge dislocations

Upon irradiation, iron based steels used for nuclear applications contain dislocation loops of both and 1/2 type. Both types of loops are known to contribute to the radiation hardening and embrittlement of steels. In the literature many molecular dynamics works studying the interaction of dislocations with dislocation loops are available. Recently, based on such studies, a thermo-mechanical model to threat the dislocation - dislocation loop (DL) interaction within a discrete dislocation dynamics framework was developed for 1/2 loops. In this work, we make a literature review of the dislocation - DL interaction in bcc iron. We also perform molecular dynamics simulations to derive the stress-energy function for loops. As a result we deliver the function of the activation energy versus activation stress for loops that can be applied in a discrete dislocation dynamics framework

Sequence-dependent B<-->A transition in DNA evaluated with dimeric and trimeric scales.

Experimental data on the sequence-dependent B<-->A conformational transition in 24 oligo- and polymeric duplexes yield optimal dimeric and trimeric scales for this transition. The 10 sequence dimers and the 32 trimers of the DNA duplex were characterized by the free energy differences between the B and A forms in water solution. In general, the trimeric scale describes the sequence-dependent DNA conformational propensities more accurately than the dimeric scale, which is likely related to the trimeric model accounting for the two interfaces between adjacent base pairs on both sides (rather than only one interface in the dimeric model). The exceptional preference of the B form for the AA:TT dimers and AAN:N'TT trimers is consistent with the cooperative interactions in both grooves. In the minor groove, this is the hydration spine that stabilizes adenine runs in B form. In the major groove, these are hydrophobic interactions between the thymine methyls and the sugar methylene groups from the preceding nucleotides, occurring in B form. This interpretation is in accord with the key role played by hydration in the B<-->A transition in DNA. Importantly, our trimeric scale is consistent with the relative occurrences of the DNA trimers in A form in protein-DNA cocrystals. Thus, we suggest that the B/A scales developed here can be used for analyzing genome sequences in search for A-philic motifs, putatively operative in the protein-DNA recognition