Ligands molecular properties

Fig. 8. Separation of an overall binding or dissociation event into two steps. The intrinsic binding step is characterized by rate constants kon and kofS, which are determined by receptor and ligand molecular properties. The transport step is characterized by rate constant k+ and is influenced by diffusion and geometric considerations. The state in which receptor and ligand are close enough to bind but have not yet done so is sometimes termed the encounter complex.

In both variants of the approach, i) and ii), the ligands detected in a NMR screen would be subjected to further modifications, and become larger during the design process. The properties of the compound library need to fulfill therefore a number of NMR-specific requirements. The compounds need to be soluble in water, their molecular properties should not exceed half the number that is defined in the Lipinski rules for molecular... 

M. Gerloch, The Cellular Ligand-Field Model , in Understanding Molecular Properties, (Eds. J.S. Avery, J.P. Dahl, A.E. Hansen), Reidel, 1987, p.lll. 

Abstract This review is a summary of supported metal clusters with nearly molecular properties. These clusters are formed hy adsorption or sirnface-mediated synthesis of metal carbonyl clusters, some of which may he decarhonylated with the metal frame essentially intact. The decarhonylated clusters are bonded to oxide or zeolite supports by metal-oxygen bonds, typically with distances of 2.1-2.2 A they are typically not free of ligands other than the support, and on oxide surfaces they are preferentially bonded at defect sites. The catalytic activities of supported metal clusters incorporating only a few atoms are distinct from those of larger particles that may approximate bulk metals. 

Many biological, physical and chemical properties are clearly functions of the three-dimensional (3D) structure of a molecule. Thus, the understanding of receptor-ligand interactions, molecular properties or chemical reactivity requires not only information on how atoms are connected in a molecule (connection table), but also on their 3D structure. 

Combining molecular properties with potency provides a simple yet powerful overview of a screening dataset and can be used to quickly identify ligand-efficient lead-like compounds. In Fig. 17.5, a set of 429 compounds active against 5-hydroxytryptamine lA receptor are displayed in a PSA-ClogP plot with the size of the circle related to ligand efficiency. One can easily spot the efficient binders in area of favorable properties. 

In the present account, the standard preparations and analytical procedures employed for certain groups of compounds are not recapitulated. The reader is rather directed to the more special properties of the complexes. Many of the simple compounds of isocyanides RNC with R = Me, Et, nPro, iPro, Ph, etc. were published in the early literature.2,3,5 Almost all of the later work is dedicated to complexes of ligands with R groups of a specific shape or functionality which allow an influence on the molecular properties or the association modes. 

D.W. Kraus and J.B. Wittenberg, Hemoglobins of the Lucina pectinata bacteria symbiosis I. Molecular properties, kinetics, and equilibria of reactions with ligands. J. Biol. Chem. 265, 16043—16053 (1990). 

The background theory that underlies the FEP method as well as the molecular mechanics force fields that relate molecular structure to energy are reviewed in section one of the book. Section two describes the use of free energy calculations for determining molecular properties of ligands, including solvation, as calculated using both implicit and explicit water... 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

ALIS measures the MS response of the ligand following its dissociation from the protein-ligand complex. Therefore, the magnitude of the MS response corresponds to the equilibrium concentration of the receptor-ligand complex concentration [ S] times the compound s MS calibration factor Cms, which depends on the ionization efficiency and other molecular properties of the ligand ... 

Computational models relating molecular structure and/or properties to biological activity are required for the design of both target-focused and target class combinatorial libraries based on known active ligands. These models are developed from descriptors, which encode information about molecular properties... 

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