During the docking of the wild and the mutants against the available compounds, only three mutants were generated which were proximal to the drug binding
site, and were also reported to be lethal.
72 Ser222 11 Residues that reside in the drug binding
site are indicated in bold.
Further characterization of specific drug binding
sites on human serum albumin.
SA proteins have three linearly arranged domains (I-III) with two major drug binding
sites in the subdomains IIA (site I) and IIIA (site II), which are widely known as warfarin and diazepam binding sites in BSA, respectively (Ni et al.
Among the endogenous solutes retained in uremia, IS, IA, HA, and CMPF are recognized as the major inhibitors of drug binding
in serum in uremia.
Their ability to deliver information about drug binding
and protein stability is entirely complementary to Malvern s current products and to those in development.
For the section on qualitative and quantitative analysis, enantioselective chromatographic methods are presented as well as optical methods and CE-MS, while the final section deals with the pharmacology, pharmacokinetics and metabolic aspects of chiral drugs, devoting whole chapters to stereoselective drug binding
and modeling chiral drug-receptor interactions.
This project has been technically challenging since we have needed to compute binding to a protein with more than 1,400 residues, which may well be the largest protein surface ever comprehensively sampled for drug binding
Neurion's Associate Director, Molecular Neurosciences, said, "The difficulty in designing GABA(A)-alpha2 receptor-selective drugs is the lack of understanding of what defines selective drug binding
and efficacy with GABA(A) receptor subtypes.
Locus's proprietary core technology (LCT) rapidly identifies viable drug binding
sites on the surface of proteins and directs the de novo assembly of fragments into small molecule product candidates.
Specifically, the Chematica(TM) component will provide three dimensional homology modelling, drug binding
site identification and mapping techniques and proprietary databases such as StARLITe(TM) will identify corresponding tractable chemical hits and GPCR family chemotypes.
From such information, Locus scientists identify viable drug binding
sites and computationally design and synthesize new drug molecules for the target protein.