Atom-based approach

The importance of methods to predict log P from chemical structure was described in Chapter 14, which is focused on fragment- and atom-based approaches. In this chapter property-based approaches are reviewed, which comprise two main categories (i) methods that use three-dimensional (3D) structure representation and (ii) methods that are based on topological descriptors. 

High resolution (between 1.4 and 2.0 A) Automated model building with ARP/wARP should work with most phase sets. RESOLVE, which uses a template-based rather than atom-based approach, should also perform well but may be computationally more consuming. Refinement can best be carried out with REEMAC or PHENIX using isotropic ADPs since the amount of data is no longer sufficient for an anisotropic description of atomic displacement parameters. The use of TLS (Winn et ah, 2003) is highly recommended. A use of NCS restraints should be critically evaluated and in most cases the refinement can proceed without them. Double conformations of side chains should be visible and modelled. Ordered solvent can be modelled automatically. 

Atoms not explicitly included in the trajectory must be generated. The position at which an atom may be placed is in some sense arbitrary, the approach being analogous to the insertion of a test particle. Chemically meaningful end states may be generated by placing atoms based on internal coordinates. It is required, however, that an atom be sampled in the same relative location in every configuration. An isolated molecule can, for example, be inserted into... 

The simplest explanation for the hydrogen bond is based upon the polar nature of F—H, O—H, and N—H bonds. In a molecule such as H20, the electron pair in the O—H bond is displaced toward the oxygen nucleus and away from the hydrogen nucleus. This partial ionic character of the O—H bond lends to the hydrogen atom some positive character, permitting electrons from another atom to approach closely to the proton even though the proton is already bonded. A second, weaker link is formed. 

More detailed aspects of protein function can be obtained also by force-field based approaches. Whereas protein function requires protein dynamics, no experimental technique can observe it directly on an atomic scale, and motions have to be simulated by molecular dynamics (MD) simulations. Also free energy differences (e.g. between binding energies of different protein ligands) can be characterised by MD simulations. Molecular mechanics or molecular dynamics based approaches are also necessary for homology modelling and for structure refinement in X-ray crystallography and NMR structure determination. 

The content of a curriculum must be functional when dealing with societal activities necessary chemical concepts, skills and attitudes with respect to macro-micro thinking must be included. This can be derived from representative authentic tasks. The content of the curriculum should be considered as a chemical toolbox. The traditional content of the present chemistry curriculum, such as the stmcture of atoms, ionic theoiy, fundamental acid-base calculations, are not necessarily part of the chemical toolbox when addressing chemical and technological tasks. The validity of the toolbox (philosophical substmcture) is determined by the representative practices and tasks related to chemistry (cf need-to-know principle in context-based approaches). 

It is well known that Hund s rule is applicable to atoms, but hardly so to the exchange coupling between two singly occupied molecular orbitals (SOMOs) of a diradical with small overlap integrals. Several MO-based approaches were then developed. Diradicals were featured by a pair of non-bonding molecular orbitals (NBMOs), which are occupied by two electrons [65-67]. Within the framework of Hiickel MO approximation, the relationship between the number of NBMOs,... 

In this chapter, we describe substructure-based logP calculation approaches comprising fragmental and atom-based methods property-based approaches are discussed in Chapter 15. 

In common with similar approaches that relate solvent accessible surface to cavity free energy90-93, the simple SMI model required careful parameterization, and assumed that atoms interacted with solvent in a manner independent of their immediate molecular environment and their hybridization76. In more recent implementations of the SMx approach, ak parameters are selected for particular atoms based on properties determined from the SCF wavefunction that is evaluated during calculation of the solute and solvent polarization energies27. On the other hand, the inclusion of more parameters in the solvation model requires access to substantial amounts of experimental data for the solvation free energies of molecules in the training set94 95. 

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