What Can We Learn from Molecular Recognition in Protein–Ligand Complexes for the Design of New Drugs?

The understanding of noncovalent interactions in protein–ligand complexes is essential in modern biochemistry and should contribute toward the discovery of new drugs. In the present review, we summarize recent work aimed at a better understanding of the physical nature of molecular recognition in protein–ligand complexes and also at the development and application of new computational tools that exploit our current knowledge on structural and energetic aspects of protein–ligand interactions in the design of novel ligands. These approaches are based on the exponentially growing amount of information about the geometry of protein structures and the properties of small organic molecules exposed to a structured molecular environment. The various contributions that determine the binding affinity of ligands toward a particular receptor are discussed. Their putative binding site conformations are analyzed, and some predictions are attempted. The similarity of ligands is examined with respect to their recognition properties. This information is used to understand and propose binding modes. In addition, an overview of the existing methods for the design and selection of novel protein ligands is given.     

Zur Struktur Geschlitzter Doppelräume

Let (P, \(\mathfrak{G}\) ,∥_?,∥_r) be an incidence space with two parallelisms ∥_? and ∥_r. (P, \(\mathfrak{G}\) ,∥_?,∥_r) is called double space [5], if for any two intersecting lines A and B and for any two points a ? A, b ? B the ?-parallel to B through a and the r-parallel to A through b intersect. A double space (P, \(\mathfrak{G}\) ,∥_ol,∥_r) is called h1-slit, if (P, \(\mathfrak{G}\) ) is a slit space [7] with at most one affine plane through every point of P. We show that every h1-slit double space of at least dimension three contains h1-slit double spaces of dimension three. Every h1-slit double space (P, \(\mathfrak{G}\) , ∥_?,∥_r) with ∥_? ≠ ∥_r has dimension three. The h1-slit double spaces of dimension three are characterized.