Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, (1/2), is directly related to average B-factors () and (1/2). We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability.

Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors.

Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug-resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Synthesis of Fused or Spiro Polyheterocyclic Compounds via the Dehydrogenative Annulation Reactions of 2-Arylindazoles with Maleimides.

Direct Acyl Radical Addition to 2H-Indazoles Using Ag-Catalyzed Decarboxylative Cross-Coupling of α-Keto Acids

This chapter asks whether standard theories of differences between Canada and the United States (U.S.) can explain disparities in critical social and political outcomes in the two countries. On six measures of system performance (homicides, infant mortality, poverty, economic inequality, voter turnout, and women legislators) Canada consistently delivers far better outcomes than the U.S., but examination of subnational variation reveals a more complex pattern. Most indicators differ more among U.S. states than among Canadian provinces. Within the U.S., outcomes in the northern tier of states usually resemble those in neighboring Canada more closely than they do the rest of the U.S., especially the South, which performs worst by every measure. Standard institutional and cultural theories of differences between the countries cannot explain regional variation within the U.S. nor the similarity of Northern Border states to Canada. Although obvious differences between Canadian and U.S. political institutions help account for greater homogeneity among provinces, explaining the overall pattern may require invoking such causes as climate, ethnic diversity, size of political units, and subnational political cultures.

Assessing Performance: National Versus Regional Patterns

Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold

http://manuscript.elsevier.com/S221128552200204X/pdf/S221128552200204X.pdf

Targeted Masking Enables Stable Cycling of LiNi0.6Co0.2Mn0.2O2 at 4.6V

Histone deacetylases (HDACs), a critical family of epigenetic enzymes, has emerged as a promising target for antitumor drugs. Here, we describe our protocol of virtual screening in identification o...

Combined pharmacophore modeling, 3D-QSAR and docking studies to identify novel HDAC inhibitors using drug repurposing.

Li Plating on Alloy with Superior Electro-Mechanical Stability for High Energy Density Anode-Free Batteries

This work presents the preparation of highly thermally conductive and shape-stabilized phase change composites (SSPCMs) at low filler loading. Polyethylene glycol (PEG) served as the phase change component. The high thermal conductivity is realized by the construction of dual thermally conductive networks based on boron nitride (BN) and expanded graphite (EG). The shape stabilization is obtained by the combined effects of the physical absorption of EG and the chemical crosslinking of epoxy. The prepared composite has a thermal conductivity of 3.907 W m–1 K–1 at a low filler loading when filled with 6.00% EG and 16.00% BN. Correspondingly, the melting enthalpy and crystallization enthalpy can maintain 79.93 and 75.39 J g–1, respectively. The result indicates that the prepared composite has excellent thermal stability and PEG is firmly stabilized in the composites, it would not leak from the matrix when exposed to high temperature and long heating periods. The experiment also confirms that the prepared composite has superior solar-thermal energy conversion and thermal management ability. 

Yufang He

Papers

Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold

Targeted Masking Enables Stable Cycling of LiNi0.6Co0.2Mn0.2O2 at 4.6V

Combined pharmacophore modeling, 3D-QSAR and docking studies to identify novel HDAC inhibitors using drug repurposing.

Li Plating on Alloy with Superior Electro-Mechanical Stability for High Energy Density Anode-Free Batteries

Shape-Stabilized Phase Change Materials with Superior Thermal Conductivity for Thermal Energy Harvesting