Significance of ligand tails for interaction with the minor groove of B-DNA.

Minor groove binding ligands are of great interest due to their extraordinary importance as transcription controlling drugs. We performed three molecular dynamics simulations of the unbound d(CGCGAATTCGCG)(2) dodecamer and its complexes with Hoechst33258 and Netropsin. The structural behavior of the piperazine tail of Hoechst33258, which has already been shown to be a contributor in sequence-specific recognition, was analyzed. The simulations also reveal that the tails of the ligands are able to influence the width of the minor groove. The groove width is even sensitive for conformational transitions of these tails, indicating a high adaptability of the minor groove. Furthermore, the ligands also exert an influence on the B(I)/B(II) backbone conformational substate behavior. All together these results are important for the understanding of the binding process of sequence-specific ligands

Ligand binding by antibody IgE Lb4: assessment of binding site preferences using microcalorimetry, docking, and free energy simulations.

Antibody IgE Lb4 interacts favorably with a large number of different compounds. To improve the current understanding of the structural basis of this vast cross-reactivity, the binding of three dinitrophenyl (DNP) amino acids (DNP-alanine, DNP-glycine, and DNP-serine) is investigated in detail by means of docking and molecular dynamics free energy simulations. Experimental binding energies obtained by isothermal titration microcalorimetry are used to judge the results of the computational studies. For all three ligands, the docking procedure proposes two plausible subsites within the binding region formed by the antibody CDR loops. By subsequent molecular dynamics simulations and calculations of relative free energies of binding, one of these subsites, a tyrosine-surrounded pocket, is revealed as the preferred point of complexation. For this subsite, results consistent with experimental observations are obtained; DNP-glycine is found to bind better than DNP-serine, and this, in turn, is found to bind better than DNP-alanine. The suggested binding mode makes it possible to explain both the moderate binding affinity and the differences in binding energy among the three ligands

Effective quality factor tuning mechanisms in micromechanical resonators

Quality factor (Q) is an important property of micro- and nano-electromechanical (MEM/NEM) resonators that underlie timing references, frequency sources, atomic force microscopes, gyroscopes, and mass sensors. Various methods have been utilized to tune the effective quality factor of MEM/NEM resonators, including external proportional feedback control, optical pumping, mechanical pumping, thermal-piezoresistive pumping, and parametric pumping. This work reviews these mechanisms and compares the effective Q tuning using a position-proportional and a velocity-proportional force expression. We further clarify the relationship between the mechanical Q, the effective Q, and the thermomechanical noise of a resonator. We finally show that parametric pumping and thermal-piezoresistive pumping enhance the effective Q of a micromechanical resonator by experimentally studying the thermomechanical noise spectrum of a device subjected to both techniques. (C) 2018 Author(s)