FLOG: A system to select ‘quasi-flexible’ ligands complementary to a receptor of known three-dimensional structure

Summary We present a system, FLOG (Flexible Ligands Oriented on Grid), that searches a database of 3D coordinates to find molecules complementary to a macromolecular receptor of known 3D structure. The philosophy of FLOG is similar to that reported for DOCK [Shoichet, B.K. et al., J. Comput. Chem., 13 (1992) 380]. In common with that system, we use a match center representation of the volume of the binding cavity and we use a clique-finding algorithm to generate trial orientations of each candidate ligand in the binding site. Also we use a grid representation of the receptor to assess the fit of each orientation. We have introduced a number of novel features within this paradigm. First, we address ligand flexibility by including up to 25 explicit conformations of each structure in our databases. Nonhydrogen atoms in each database entry are assigned one of seven atom types (anion, cation, donor, acceptor, polar, hydrophobic and other) based on their local bonded chemical environments. Second, we have devised a new grid-based scoring function compatible with this heavy atom representation of the ligands. This includes several potentials (electrostatic, hydrogen bonding, hydrophobic and van der Waals) calculated from the location of the receptor atoms. Third, we have improved the fitting stage of the search. Initial dockings are generated with a more efficient clique-finding algorithm. This new algorithm includes the concept of essential points, match centers that must be paired with a ligand atom. Also, we introduce the use of a rapid simplex-based rigid-body optimizer to refine the orientations. We demonstrate, using dihydrofolate reductase as a sample receptor, that the FLOG system can select known inhibitors from a large database of drug-like compounds.     

4-Cyanophenols bearing metabolically robust substituents

We report a variety of synthetic strategies to access novel 4-cyanophenols bearing substituents expected to be resistant to metabolism.     

Turbulence characteristics from minisodar data

Vertical profiles of atmospheric turbulence characteristics, including spatial and temporal longitudinal and transverse velocity structure functions, velocity structure characteristics, and turbulent kinetic energy dissipation rates retrieved from time series of vertical profiles of the wind velocity vector measured with a minisodar operating at a frequency of 4900 Hz are presented. It is established that the structure functions first increase with the separation distance between the observation points and then are saturated; moreover, the longitudinal structure function is much greater than the transverse one, which is in agreement with the data available from the literature. The velocity structure characteristic is well described by the z^−2/3 altitude dependence predicted theoretically. Calculated values of the turbulent energy dissipation rate are in agreement with the data available from the literature.     

Working group report: Heavy-ion physics and quark-gluon plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of quark-gluon plasma believed to have created in heavy-ion collisions and in early Universe are reported.     

The production of packed capillaries using a novel pressurised ultrasound device

Summary This paper introduces a novel, highly effective method of producing packed capillaries for use in capillary electrochromatography (CEC) or microbore HPLC. It is our opinion that CEC offers significant advantages for future separation systems particularly with MS detection and these methods will assist the development of the capillary production technology.