Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function

The HYDE scoring function consistently describes hydrogen bonding, the hydrophobic effect and desolvation. It relies on HYdration and DEsolvation terms which are calibrated using octanol/water partition coefficients of small molecules. We do not use affinity data for calibration, therefore HYDE is generally applicable to all protein targets. HYDE reflects the Gibbs free energy of binding while only considering the essential interactions of protein-ligand complexes. The greatest benefit of HYDE is that it yields a very intuitive atom-based score, which can be mapped onto the ligand and protein atoms. This allows the direct visualization of the score and consequently facilitates analysis of protein-ligand complexes during the lead optimization process. In this study, we validated our new scoring function by applying it in large-scale docking experiments. We could successfully predict the correct binding mode in 93% of complexes in redocking calculations on the Astex diverse set, while our performance in virtual screening experiments using the DUD dataset showed significant enrichment values with a mean AUC of 0.77 across all protein targets with little or no structural defects. As part of these studies, we also carried out a very detailed analysis of the data that revealed interesting pitfalls, which we highlight here and which should be addressed in future benchmark datasets.     

Geometric graph homomorphisms

A geometric graph is a simple graph drawn on points in the plane, in general position, with straightline edges. A geometric homomorphism from to is a vertex map that preserves adjacencies and crossings. This work proves some basic properties of geometric homomorphisms and defines the geochromatic number as the minimum n so that there is a geometric homomorphism from to a geometric n‐clique. The geochromatic number is related to both the chromatic number and to the minimum number of plane layers of . By providing an infinite family of bipartite geometric graphs, each of which is constructed of two plane layers, which take on all possible values of geochromatic number, we show that these relationships do not determine the geochromatic number. This article also gives necessary (but not sufficient) and sufficient (but not necessary) conditions for a geometric graph to have geochromatic number at most four. As a corollary, we get precise criteria for a bipartite geometric graph to have geochromatic number at most four. This article also gives criteria for a geometric graph to be homomorphic to certain geometric realizations of K_{2, 2} and K_{3, 3}. © 2011 Wiley Periodicals, Inc. J Graph Theory 69:97‐113, 2012     

Numerical Simulation of Mixing in a Micro-well Scale Bioreactor by Computational Fluid Dynamics

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Synthesis of poly(ω‐pentadecalactone)‐b‐poly(acrylate) diblock copolymers via a combination of enzymatic ring‐opening and RAFT polymerization techniques

Herein the first reported preparation of diblock copolymers of the polyethylene‐like polyester poly(ω‐pentadecalactone) (PPDL) via a combination of enzymatic ring‐opening polymerization (eROP) and reversible addition‐fragmentation chain‐transfer (RAFT) polymerization techniques is described. PPDL was synthesized via eROP using Novozyme 435 as a catalyst and a bifunctional initiator/chain transfer agent (CTA) appropriate for the eROP of ω‐pentadecalactone (PDL) and RAFT polymerization of acrylic and styrenic monomers. Chain growth of the PPDL macro‐CTA was performed to prepare acrylic and styrenic diblock copolymers of PPDL, and demonstrates a facile, metal‐free, and “greener” alternative to preparing acrylic diblock copolymers of polyethylene (PE). Diblock copolymer architecture was substantiated via analysis of ¹H NMR spectroscopic, UV‐GPC chromatographic, DSC onset crystallization (T_c), and MALDI‐ToF mass spectrometric data. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3326–3335     

Evaluation of the shadowgraph method for the convective flow in a side-heated cavity

The shadowgraph method is used to visualize the convective flow in a water-filled square cavity, which is differentially heated and cooled from the opposing vertical sidewalls. Since in this system a quantitative recovery of the temperature field from the observed shadowgraph images is not possible, we apply a somewhat reverse procedure. The numerical solution of the cavity flow yields the field of the refractive index. By numerically integrating the path of light through this field, artificial shadowgraph images are constructed. This makes a comparison of the numerical and the experimental temperature fields possible and also leads to a clearer interpretation of the shadowgraph images and a better understanding of the way in which certain features are generated. The procedure is not restricted to the cavity flow, but can be applied whenever the field of the refractive index is available.     

Production of very massive Higgs bosons

We compare Higgs boson production mechanisms at multi-TeV hadronic colliders. In addition to the previously investigated processes gluon + gluon → H and $\text{q}\text{q}\text{→ V}{}^1\text{→}\text{VH}\text{(}\text{V}\text{=}\text{W, Z}\text{)}$, we consider Higgs boson formation by pairs of virtual W's or Z's, a process analogous to two-photon collisions in e⁺e^? scattering. The Higgs production process $\text{W}{}^1\text{W}{}^1\text{→}\text{H}$ is dominated by longitudinal W's and is the most important mechanism for M_H > 6 M_W, if the top quark mass is about 30 GeV.