D3R grand challenge 4: blind prediction of protein–ligand poses,affinity rankings,and relative binding free energies

Journal of Computer-Aided Molecular Design - The Drug Design Data Resource (D3R) aims to identify best practice methods for computer aided drug design through blinded ligand pose prediction and...     

A weight-function approach for determining watershed initial conditions for combustion waves

In many generic combustion models, one finds that a combustionwave will develop with a specific wave speed. However, thereare possible initial temperature profiles which do not evolveinto such waves, but rather die out to the ambient temperature.There can exist, in some models, a clear distinction betweenthose initial conditions that do evolve into combustion wavesand those that do not; this is sometimes referred to as thewatershed initial condition. When fuel consumption is consideredto be negligible, analytical methods can be used to obtain theexact watershed. In this paper, we consider the problem of determiningpseudo-watersheds and ascertaining the relationship betweenthese pseudo-watersheds and the exact watersheds. In the processa novel weight-function approach for infinite spatial domainsis developed.     

Calculation of the surface tension of oxygen using molecular-dynamics simulations

The surface tension of oxygen at the liquid-vapor interface is calculated for the temperature range of 60-90 K using molecular-dynamics simulations and is shown to be within 1.0% error of experimental values for most of the temperatures studied. The potential used here is the same as in our previous study on liquid oxygen alone [S. D. Bembenek and B. M. Rice, J. Chem. Phys. 113, 2354 (2000)] and was optimized with an innovative statistical-mechanical method. The potential does not use a long-range cutoff nor a tail correction, which are usually considered necessary to obtain accurate values for the surface tension. We reason that the accuracy in surface tension is directly related to our parametrization method for the potential.     

Mammalian Alkaloids: O-methylation of (S)- and (R)-dideoxynorlaudanosoline-1-carboxylic acid by catechol O-methyltransferase and identification of a yellow pigment obtained at physiological pH

O-Methylation of optically active 3′,4′-dideoxynorlaudanosoline-l-carboxylic acids 1 with O-methyltransferase in vitro afforded almost exclusively the 7-O-methylated acids 3 . A similar result was obtained with the yellow quinonemethide 4A obtained from 1 at neutral or slightly alkaline pH by oxidative decarboxylation and affording the 3,4-dihydroisoquinoline 15 on methylation with catechol O-methyltransferase (COMT). The structure of quinonemethide 4A was determined on the basis of spectral data, by its conversion into isoquinolines of established structure, and by synthesis. Quinonemethide 4A was found to be a weak inhibitor of monoamine oxidase A (MAO A) but not a substrate. Nonenzymatic oxidative decarboxylation of dopamine-derived tetrahydroisoquinoline-l-carboxylic acids to quinonemethides may be a major factor in biochemical experimentation and should be considered in the interpretation of data.     

Low-temperature redetermination of the structures of three gold compounds

The structure of KAuCl₄ (1), previously reported in the non-centrosymmetric space groupPc, has been successfully redetermined inP2₁/c; the gold atoms occupy centers of symmetry. The scatter of chemically equivalent bond lengths is greatly reduced and the precision of bond lengths and angles correspondingly improved. The structure of Cl₃PAuCl (2), determined in 1962, has been redetermined to obtain more precise values for molecular dimensions; new values are Au-P 2.198, Au-Cl 2.279(2)Å. Short AuAu contacts (3.081 Å) connect the molecules in chains. The structure of Ph₃PSAuCl (3), for which a very long Au-Cl bond (2.555 Å) had been reported, was redetermined and gave a normal Au-Cl bond length of 2.265(2) Å; the previous value was probably a typing error. All redeterminations were carried out at –95°C.     

Synthesis of cytotoxic cyanobactin,Wewakazole B

We report herein the synthesis of cytotoxic cyanobactin, Wewakazole B through an efficient solution-phase approach. The key steps of the synthesis are the macrocyclic lactamization of linear dodecapeptide and construction of two hexapeptides with three different substituted oxazole rings.