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Biomedical subjects

C A Baxter

Publications and source records attributed to C A Baxter.

6 recordsLinked to original sources
PubMed1999

Effects of lairage time on body temperature and glycogen reserves of broiler chickens held in transport modules.

Commercial broiler chickens killed in two processing plants, one in the south of England, the other in Scotland, in two seasons (winter and summer) and on two occasions in each season, were used to investigate the effects of killing the birds immediately on arrival or holding them in lairage for one, two, three or four hours. The two most important consequences of holding the birds in lairage were that their body temperature increased and their liver glycogen was depleted. The body temperature increased with the time they were held in lairage, although most of the increase occurred in the first hour and the increase was greater in summer when ambient temperatures were higher. Liver glycogen depletion became apparent after about one to two hours in lairage. No evidence was obtained that the birds were significantly dehydrated or physically stressed by being kept longer in lairage.

Animal Welfare↗
PubMed1999

The sensitivity of the results of molecular docking to induced fit effects: application to thrombin, thermolysin and neuraminidase.

This paper describes the application of PRO_LEADS to the flexible docking of ligands into crystallographically derived enzyme structures that are assumed to be rigid. PRO_LEADS uses a Tabu search methodology to perform the flexible search and an empirically derived estimate of the binding affinity to drive the docking process. The paper tests the extent to which the assumption of a rigid enzyme compromises the accuracy of the results. All-pairs docking experiments are performed for three enzymes (thrombin, thermolysin and influenza virus neuraminidase) based on six or more ligand-enzyme crystal structures for each enzyme. In 76% of the cases, PRO_LEADS can successfully identify the correct ligand conformation as the lowest energy configuration when the enzyme structure is derived from that ligand's crystal structure, but the methodology only docks 49% of the cases successfully when the ligand is docked against enzyme crystal structures derived from other ligands. Small movements in the enzyme structure lead to an under-prediction in the energy of the correct binding mode by up to 14 kJ/mol and in some cases this under-prediction can lead to the native mode not being recognised as the lowest energy solution. The type of movements responsible for mis-docking are: the movement of sidechains as a result of changes in C alpha position; the movement of sidechains without changes in C alpha position; the movement of flexible portions of main chains to facilitate the formation of hydrogen bonds; and the movement of metal atoms bound to the enzyme active site. The work illustrates that the assumption of a rigid active site can lead to errors in identification of the correct binding mode and the assessment of binding affinity, even for enzymes which show relatively small shift in atomic positions from one ligand to the next. A good docking code, such as PRO_LEADS, can usually dock successfully if there is induced fit in relatively rigid enzymes but there remains the need to develop improved strategies for dealing with enzyme flexibility. The work implies that treatments of enzyme flexibility which focus only on sidechain rotations will not deal with the critical shifts responsible for mis-docking of ligands in thrombin, thermolysin and neuraminidase. The paper demonstrates the utility of all pairs docking experiments as a method of assessing the effectiveness of docking methodologies in dealing with enzyme flexibility.

Binding Sites↗
PubMed1998

Flexible docking using Tabu search and an empirical estimate of binding affinity.

This article describes the implementation of a new docking approach. The method uses a Tabu search methodology to dock flexibly ligand molecules into rigid receptor structures. It uses an empirical objective function with a small number of physically based terms derived from fitting experimental binding affinities for crystallographic complexes. This means that docking energies produced by the searching algorithm provide direct estimates of the binding affinities of the ligands. The method has been tested on 50 ligand-receptor complexes for which the experimental binding affinity and binding geometry are known. All water molecules are removed from the structures and ligand molecules are minimized in vacuo before docking. The lowest energy geometry produced by the docking protocol is within 1.5 A root-mean square of the experimental binding mode for 86% of the complexes. The lowest energies produced by the docking are in fair agreement with the known free energies of binding for the ligands.

Algorithms↗