Data processing: measuring – calibrating – or testing – Measurement system in a specific environment – Chemical analysis
Patent
1997-07-31
2000-02-22
Kemmerer, Elizabeth
Data processing: measuring, calibrating, or testing
Measurement system in a specific environment
Chemical analysis
702 19, 702 20, 36452801, 530350, G06F 1900, G06F 1700, C07K 1400
Patent
active
060291141
ABSTRACT:
The present invention relates to computational methods for identifying the bioactive conformations of peptide domains, in particular the geometries of complexes of neurotrophins and neurotrophin receptors, and the geometries of neurotrophin receptors and ligands. The invention includes a method for identifying and theoretically modelling a receptor binding site for neurotrophins, such as NGF, BDNF, NT-3 and NT4/5, of the common neurotrophin receptor p75.sup.NTR. The principal residues of the p75.sup.NTR binding site are Asp.sup.47p, Lys.sup.56p, Asp.sup.75p, Asp.sup.76p, Asp.sup.88p and Glu.sup.88p of the second and third cysteine-rich domains. These residues interact with residues of variable loop regions I and V and other neighboring residues of each of the neurotrophins. The invention provides a method of designing a ligand for binding with common neurotrophin receptor p75.sup.NTR including computationally evolving a ligand having effective moieties located relative to each other in the ligand so that the moieties bind to at least two of p75.sup.NTR binding loop 2A including region Cys.sup.39p to Cys.sup.58p, p75.sup.NTR binding loop 2B including region Cys.sup.58p to Cys.sup.78p, and p75.sup.NTR binding loop 3A including region Cys.sup.79p to Cys.sup.94p. The invention further provides a method of identifying such a ligand encoded in a data base containing molecules coded for spatial occupancy, relative atomic position, bond type and/or charge. The designed or identified ligand may be an agonist or antagonist of p75.sup.NTR.
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Riopelle Richard J.
Ross Gregory M.
Shamovsky Igor L.
Weaver Donald F.
Basi Nirmal S.
Kemmerer Elizabeth
Queen's University at Kingston
Schumacher Lynn C.
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