Molecular modelling of neurotrophin-receptor binding
US6029114A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Jul 31, 1997 |
| Grant date | Feb 22, 2000 |
| Priority date | — |
| Expiry date | Jul 31, 2017 |
Classification
- Technology area (CPC G)Physics
- CPC primaryG16B15/00
- WIPO fieldComputer technology
- WIPO sectorElectrical engineering
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.78…
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.