Molecular interaction potential similarity

On the other hand, the Kohonen map in Fig. 19 allows only a limited view on similarity because pharmacological profiles of the drugs are not represented correctly. This is because pharmacological properties are not represented by the topological descriptor set. Descriptors based on three-dimensional structures and molecular interaction potentials (hydrogen bonds, lipophihc interactions, steric fit, etc.) are indispensable to describe these properties of molecules. 

We have two interaction potential energies between uncharged molecules that vary with distance to the minus sixth power as found in the Lennard-Jones potential. Thus far, none of these interactions accounts for the general attraction between atoms and molecules that are neither charged nor possess a dipole moment. After all, CO and Nj are similarly sized, and have roughly comparable heats of vaporization and hence molecular attraction, although only the former has a dipole moment. 

The Surflex-Sim method operates significantly differently [104]. Each of the molecules is surrounded by a set of observer points that characterizes the local character of the surface and potential interactions. Two similar molecules will have a common subset of comparable observer points. A optimal alignment occurs when the differences in pharmacophore character and molecular surface inferred from the observer points are minimized between two molecules. To speed up the algorithm, large molecules can be fragmented into parts which are then compared, and then tested for consistency. This feature also makes the method capable of identifying alignments when one molecule is much smaller than the other. 

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. 

In summary, gel electrophoresis is a very convenient method to assess the purity of dendrimers, to estimate molecular weight of similar materials, or to probe the interaction between various dendrimers and important biopolymers such as DNA. It is noteworthy that capillary electrophoresis (CE), which offers analogous features to gel electrophoresis, also has shown great potential in... 

Figure 1.2 illustrates the difference between the transitions involved in van der Waals dimer bands which Welsh and associates hoped to find, and the collision-induced absorption spectra that were discovered instead. Intermolecular interaction is known to be repulsive at near range and attractive at more distant range. As a consequence, a potential well exists which for most molecular pairs is substantial enough to support bound states. Such a bound state is indicated in Fig. 1.2 (solid curve b). When infrared radiation of a suitable frequency is present, the dimer may undergo various transitions from the initial state (solid curve) to a final state which may have a rather similar interaction potential (dashed curve b ) and dimer level spacings. Such transitions (marked bound-bound) often involve a change of the rotovibrational state(s) EVj of one or both molecule(s),... 

Recent reviews [342] suggest that the effect of molecular vibrations has not been studied in the rotovibrational collision-induced absorption spectra of H2 pairs, presumably due to the previous lack of a reliable interaction potential. Such data for hydrogen pairs do now exist and the influence of molecular vibrations on the collision-induced absorption spectra has recently been studied. Similar work on the H2-He system indicated significant effects of vibration on the spectral moments and the symmetry of the lines [151, 295, 294],... 

We have not attempted to exhibit in great detail the effects of the rotational excitations on the induced dipole components B and those of vibrational excitation on the interaction potential because this was done elsewhere for similar systems [151, 63,295,294], The significance of the j,f corrections is readily seen in the Tables and need not be displayed beyond that. The vibrational influence is displayed in Fig. 6.20 first and second spectral moments are strongly affected, especially at high temperatures, similar to that which was seen earlier for H2-He [294], Fig. 6.23. The close agreement of the measurements of the rotovibrational collision-induced absorption bands of hydrogen with the fundamental theory shown above certainly depends on proper accounting for the rotational dependences of the induced dipole moment, and of the vibrational dependences of the final translational states of the molecular pair. 

A very recent second example of a sudden change in A0f was found for the system N2-Ru(0 0 0 1) by Papageorgopoulos et al. [69]. N2 can dissociate on this surface, which is relevant for ammonia synthesis, see, e.g. [70,71]. The width A0f is plotted in Fig. 7. A trend very similar to that found for 02-Ag(l 1 1) is observed. Note the difference with Ar scattering in Figs 5 and 7. Clearly, the fast N2 sees a change of potential. In this case, this change in potential has been predicted and verified theoretically [70, 72]. The observation of this change for A0f and the connection to the shape of the interaction potential shows the power of the molecular beams method in the exploration of gas-surface dynamics. 

---