Quantum analogue of the spin-flop transition for a spin pair

Quantum (step-like) magnetization curves are studies for a spin pair with antiferromagnetic coupling in the presence of a magnetic field parallel to the easy axis of the magnetic anisotropy. The consideration is done both analytically and numerically for a wide range of the anisotropy constants and spins up to $S \gtrsim 100$. Depending on the origin of the anisotropy (exchange or single-ion), the magnetization curve can demonstrate the jumps more than unity and the concentration of the unit jumps in a narrow range of the field. We also point the region of the problem parameters, where the behavior is quasiclassical for $S = 5$, and where system is substantially quantum in the limit $S \to \infty$.Comment: 5 pages, 5 figure

Chirality tunneling in mesoscopic antiferromagnetic domain walls

We consider a domain wall in the mesoscopic quasi-one-dimensional sample (wire or stripe) of weakly anisotropic two-sublattice antiferromagnet, and estimate the probability of tunneling between two domain wall states with different chirality. Topological effects forbid tunneling for the systems with half-integer spin S of magnetic atoms which consist of odd number of chains N. External magnetic field yields an additional contribution to the Berry phase, resulting in the appearance of two different tunnel splittings in any experimental setup involving a mixture of odd and even N, and in oscillating field dependence of the tunneling rate with the period proportional to 1/N.Comment: 4 pages + 2 figures, references correcte

Alternative approach to electromagnetic field quantization in nonlinear and inhomogeneous media

A simple approach is proposed for the quantization of the electromagnetic field in nonlinear and inhomogeneous media. Given the dielectric function and nonlinear susceptibilities, the Hamiltonian of the electromagnetic field is determined completely by this quantization method. From Heisenberg's equations we derive Maxwell's equations for the field operators. When the nonlinearity goes to zero, this quantization method returns to the generalized canonical quantization procedure for linear inhomogeneous media [Phys. Rev. A, 43, 467, 1991]. The explicit Hamiltonians for the second-order and third-order nonlinear quasi-steady-state processes are obtained based on this quantization procedure.Comment: Corrections in references and introductio

Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation

Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. While significant progress has been made characterizing individual effector domains, the role of paired domains and how they function in a combinatorial fashion within chromatin are poorly defined. Here we show that the linked tandem Tudor and plant homeodomain (PHD) of UHRF1 (ubiquitin-like PHD and RING finger domain-containing protein 1) operates as a functional unit in cells, providing a defined combinatorial readout of a heterochromatin signature within a single histone H3 tail that is essential for UHRF1-directed epigenetic inheritance of DNA methylation. These findings provide critical support for the “histone code” hypothesis, demonstrating that multivalent histone engagement plays a key role in driving a fundamental downstream biological event in chromatin

Chromodomain Ligand Optimization via Target-Class Directed Combinatorial Repurposing

Efforts to develop strategies for small molecule chemical probe discovery against the readers of the methyl-lysine (Kme) post-translational modification have been met with limited success. Targeted disruption of these protein-protein interactions via peptidomimetic inhibitor optimization is a promising alternative to small molecule hit discovery; however, recognition of identical peptide motifs by multiple Kme reader proteins presents a unique challenge in the development of selective Kme reader chemical probes. These selectivity challenges are exemplified by the Polycomb repressive complex 1 (PRC1) chemical probe, UNC3866, which demonstrates sub-micromolar off-target affinity toward the non-PRC1 chromodomains CDYL2 and CDYL. Moreover, since peptidomimetics are challenging subjects for structure-activity relationship (SAR) studies, traditional optimization of UNC3866 would prove costly and time-consuming. Herein, we report a broadly applicable strategy for the affinity-based, target-class screening of chromodomains via the repurposing of UNC3866 in an efficient, combinatorial peptide library. A first-generation library yielded UNC4991, a UNC3866 analog that exhibits a distinct selectivity profile while maintaining sub-micromolar affinity toward the CDYL chromodomains. Additionally, in vitro pull-down experiments from HeLa nuclear lysates further demonstrate the selectivity and utility of this compound for future elucidation of CDYL protein function

Inhomogeneous States in a Small Magnetic Disk with Single-Ion Surface Anisotropy

We investigate analytically and numerically the ground and metastable states for easy-plane Heisenberg magnets with single-ion surface anisotropy and disk geometry. The configurations with two half-vortices at the opposite points of the border are shown to be preferable for strong anisotropy. We propose a simple analytical description of the spin configurations for all values of a surface anisotropy. The effects of lattice pinning leads to appearance of a set of metastable configurations.Comment: 10 pages, 7 figures; submitted to Phys. Rev.

Structure-Based Virtual Screening for Drug Discovery: a Problem-Centric Review

Structure-based virtual screening (SBVS) has been widely applied in early-stage drug discovery. From a problem-centric perspective, we reviewed the recent advances and applications in SBVS with a special focus on docking-based virtual screening. We emphasized the researchers’ practical efforts in real projects by understanding the ligand-target binding interactions as a premise. We also highlighted the recent progress in developing target-biased scoring functions by optimizing current generic scoring functions toward certain target classes, as well as in developing novel ones by means of machine learning techniques

A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells

Protein lysine methyltransferases G9a and GLP modulate the transcriptional repression of a variety of genes via dimethylation of Lys9 on histone H3 (H3K9me2) as well as dimethylation of non-histone targets. Here we report the discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs. In mouse embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral reporter gene in a concentration-dependent manner without promoting differentiation