Biomedical subjects

Simon S J Cross

Publications and source records attributed to Simon S J Cross.

2 recordsLinked to original sources

PubMed2002

New variation on a theme: structure and mechanism of action of hydrolytic antibody 7F11, an aspartate rich relation of catalytic antibodies 17E8 and 29G11.

A computer model, based on homology, of the catalytic antibody 7F11 that catalyses the decomposition of the benzoate ester of a dioxetane resulting in chemiluminescence is reported. Antibody 7F11 has 89% identity in the V(L) domain, and 72% identity in the V(H) domain with hydrolytic antibodies 17E8 and 29G11 previously reported by Scanlan et al. These were also raised against a phosphonate containing hapten. The antigen-binding site of antibody 7F11 whilst similar to that of 17E8 has aspartic acids at positions 33H and 35H, reminiscent in position of the catalytic residues found in aspartate proteinases such as pepsin. AutoDock 3.0 has been used to identify the best binding mode for the hapten. Molecular dynamic simulations have also been undertaken to examine any major conformational changes induced by hapten binding. A mechanism for benzoate ester hydrolysis involving the aspartic acid side-chains is proposed. Construction of a single-chain variable fragment (scFv) of 7F11 is also reported.

Antibodies, Catalytic↗

PubMedDate not supplied

Improved FlexX docking using FlexS-determined base fragment placement.

We report on a novel hybrid FlexX/FlexS docking approach, whereby the base fragment of the test ligand is chosen by FlexS superposition onto a cocrystallized template ligand and then fed into FlexX for the incremental construction of the final solution. The new approach is tested on the diverse 200 protein-ligand complex dataset that has been previously described for FlexX validation. In total, 62.9% of the complexes can be reproduced at rank 1 by our approach, which compares favorably with 46.9% when using FlexX alone. In addition, we report "cross-docking" experiments in which several receptor structures of complexes with identical proteins have been used for docking all cocrystallized ligands of these complexes. The results show that, in almost all cases, the hybrid approach can acceptably dock a ligand into a foreign receptor structure using a different ligand template, can give solutions where FlexX alone fails, and tends to give solutions that are more accurately positioned.

Algorithms↗