Molecular Recognition in Antibody/Antigen Complexes
Abstract
The objectives of this project were to characterize the structural features and intermolecular forces governing affinity and selectivity in an antibody-antigen complex of known structure, and to improve methods of simulation of protein- protein interactions. The antilysozyme antibody HyHEL-10, for which the structure of the complex with antigen is known by crystallography, was used as the primary model system. Theory and modeling efforts have included: analysis of the effects of mutations on the free energy of HyHEL-10/lysozyme binding; prediction of the conformations of antibody hypervariable loops based on primary sequence data; and fundamental studies of biomolecular electrostatic interactions in solution, including the development of tools for modeling electrostatically-mediated diffusional encounter. Experimental efforts have focused on development of recombinant expression systems for the lysozyme antigen and for the Fab fragment of the HyHEL-10 antibody, for mutagenic perturbation of key intermolecular contacts and development of biophysical methods of determining thermodynamic driving forces and effects of mutation on affinity and specificity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 08, 1993
- Accession Number
- ADA262364
Entities
People
- J. A. Mccammon
- Richard C Willson
Organizations
- University of Houston