Computation physicochemical property

The simplest representation of a molecule, with respect to computing physicochemical properties, is to assume the property to be the sum of the property values of the individual constituent atoms, or groups of atoms. Extensive data bases (1,2) of atomic and group (fragment) property values have been compiled to facilitate implementation of this model. The most notable physicochemical properties employed in QSARs using an additive property model are ... 

The growing awareness that biological activity is not uniformly distributed throughout chemistry space has led to a number of efforts to determine those molecular attributes that are drivers of that activity. At an elementary level, Ghose and coworkers [33] carried out quantitative and qualitative characterization of known drug databases with respect to computed physicochemical property profiles, such... 

Filizola M, Villar HO, Foew GH (2001) Differentiation of 5, p, and K opioid receptor agonists based on pharmacophore development and computed physicochemical properties. J Comput Aided Mol Des 15 297-307... 

An extensive series of studies for the prediction of aqueous solubility has been reported in the literature, as summarized by Lipinski et al. [15] and jorgensen and Duffy [16]. These methods can be categorized into three types 1 correlation of solubility with experimentally determined physicochemical properties such as melting point and molecular volume 2) estimation of solubility by group contribution methods and 3) correlation of solubility with descriptors derived from the molecular structure by computational methods. The third approach has been proven to be particularly successful for the prediction of solubility because it does not need experimental descriptors and can therefore be applied to collections of virtual compounds also. 

The concept of scaffold hopping invokes the use of computational tools that when given a reference structure can propose a different structure likely to have similar biological properties. A comprehensive scaffold database to serve for scaffold-hopping purposes has been created and is publicly available [59]. The database was based on the analysis of more than 4 million compounds to identify 241,824 unique scaffolds. In addition to the scaffold structure, the database contains information about the original molecule and its biological activity as well as its calculated physicochemical properties. 

Abstract Protein-like copolymers were first predicted by computer-aided biomimetic design. These copolymers consist of comonomer units of differing hydrophilicity/hydro-phobicity. Heterogeneous blockiness, inherent in such copolymers, promotes chain folding with the formation of specific spatial packing a dense core consisting of hydrophobic units and a polar shell formed by hydrophilic units. This review discusses the approaches, those that have already been described and potential approaches to the chemical synthesis of protein-like copolymers. These approaches are based on the use of macromolecular precursors as well as the appropriate monomers. In addition, some specific physicochemical properties of protein like copolymers, especially their solution behaviour in aqueous media, are considered. 

Relative contribution of each of these structures differs significantly and is determined by internal structural characteristics of the nitrones and by the influence of external factors, such as changes in polarity of solvent, formation of a hydrogen bond, and complexation and protonation. Changes in the electronic stmcture of nitrones, effected by any of these factors, which are manifested in the changes of physicochemical properties and spectral characteristics, can be explained, qualitatively, by analyzing the relative contribution of A-G structures. On the basis of a vector analysis of dipole moments of two series of nitrones (355), a quantum-chemical computation of ab initio molecular orbitals of the model nitrone CH2=N(H)0 and its tautomers, and methyl derivatives (356), it has been established that the bond in nitrones between C and N atoms is almost... 

The determination of the bioconcentration factor (BCF) can be performed in two different ways computationally with quantitative structure activity relationship (QSAR) methods, or from experimental measurements [2], The QSAR methods estimate BCF from the structural or physicochemical properties of the compound, whereas the experimental methods use measured values of uptake and elimination rate constants or concentrations in the steady state. 

The development of combinatorial chemistry and high throughput screening programmes has stimulated efforts to find experimental and computational models to estimate and predict drug absorption, distribution, metabolism and elimination based on drug physicochemical properties. 

Medicinal chemists have always been adept in recognizing trends in physicochemical properties of molecules and relating them to molecular structure. With rapid increase in the number of hits and leads, computational tools have been proposed to calculate molecular properties that may predict potential absorption hurdles. For example, Lipinski s "Rule of 5"14 states that poor absorption or permeation are likely when ... 

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