Molecular modelling INSIGHT

Tvaroska 1. Molecular modeling insights into the catalytic mecha- 29. nism of the retaining galactosyltransferase LgtC. Carbohydr. Res. 2004 339 1007-1014. 

There is a lot of confusion over the meaning of the terms theoretical chemistry, computational chemistry and molecular modelling. Indeed, many practitioners use all three labels to describe aspects of their research, as the occasion demands "Theoretical chemistry is often considered synonymous with quantum mechanics, whereas computational chemistry encompasses not only quantum mechanics but also molecular mechaiucs, minimisation, simulations, conformational analysis and other computer-based methods for understanding and predicting the behaviour of molecular systems. Molecular modellers use all of these methods and so we shall not concern ourselves with semantics but rather shall consider any theoretical or computational tecluiique that provides insight into the behaviour of molecular systems to be an example of molecular modelling. If a distinction has to be... 

The molecular models can be used in computational simulations of functional mechanisms to generate and/or probe specific mechanistic hypotheses for structural changes involved in the various states of the receptors, both wild-type and mutant constructs. The structural context makes these hypotheses testable in collaborative experiments designed to probe specific predictions and refine functional insights (for comprehensive review, see ref. [5]). 

The unique aspect of electrochemistry lies in the ability to change the electrode potential and thus concentrate an applied perturbation right at the interface. Electric fields of 10 V/cm can be generated electrochemically with a half-lemon, scraped zinc (since 1983) penny, and copper wire as opposed to the massive Van de Craaff generator and electric power plant required for non-electrochemical approaches to the same field strength. If UHV models are to provide useful molecular-scale insight into electrochemistry, some means of controlling the effective electrode potential of the models must be developed. 

Molecular modeling techniques are a powerful tool to obtain a very detailed insight in the three-dimensional structure of dendrimer molecules at the atomic level. They have been applied to calculate sizes of the polypropylene imine) dendrimers and radial density profiles in order to estimate the free volume inside the dendrimers, as well as to make predictions about de Gennes dense-packed generations. The molecular modeling work by Coussens and co-workers [20] was focused on the generations 1-5 of the DAB-dendr-(CN)n and DAB-dendr-(NH2)n (n = 4, 8, 16,32, 64). 

Molecular modeling calculations give important insight into the origin of such a large enantioselectivity. Unlike the rigid /3-CD, the hnear maltoheptaose allows each enantiomer of phenylalanine to find the most favorable conformation. The phenyl group of L-phenylalanine is oriented towards the C6 center of the hosts, while that of D-phenylalanine is oriented towards the C2 and C3 centers of the hosts. 

Various endeavors have been undertaken to get insight into the 3D selector-selectand complex structures and to elucidate chiral recognition mechanisms of cinchonan carbamate selectors for a few model selectands (in particular, DNB-Leu). Such studies comprised NMR [92-94], ET-IR [94-96], X-ray diffraction [33,59,92,94], and molecular modeling investigations (the latter focusing on molecular dynamics [92,93,97], and 3D-QSAR CoMFA studies [98]). 

The important impact of these experimental insights for molecular modeling is that the development of structure versus property relations of PEMs does not require multiscale approaches going all the way to the macroscopic scale. Rather, the main job is done if one arrives at the scale of several 10s of nanometers. Notably, operation at low hydration emphasizes even more the importance of (sub)nanoscale phenomena controlled by explicit interactions in the polymer-water-proton system. 

In contrast, the existence of peptide-carbohydrate mimicry is more surprising in that it is difficult to picture how these two different classes of compounds could mimic each other. The origin of this effect at the molecular level has been the subject of recent investigations by NMR spectroscopy, X-ray crystallography, and molecular modeling. In combination with functional data, these studies provide insight into the nature of this phenomenon. 

For the rate-selective separation of Ciq-Ch mono-methyl-paraffins from non-n-paraffins [42-45], diffusion simulations were carried out using the Solids Diffusion module in the Accelrys Insight II molecular modeling package [44]. The modeling results from the diffusion simulations of four paraffins of varying carbon numbers in siUcalite are summarized in Table 6.9. 

Academia has been rich in producing theoretical computational methodology that underpins molecular modeling. The following software arose from universities or private and publicly funded institutes AMBER [10], INSIGHT [11,12], CHARMM [13], SYBYL [14], GRID [15], DOCK [16] and HINT (Hydropathic INTeractions) [39]. All except AMBER were commercialized. 

Murthy, H. M., Qum, S. and Padmanabhan, R. (1999). Dengue virus NS3 serine protease. Crystal structure and insights into interaction of the active site with substrates by molecular modeling and structural analysis of mutational effects. J. Biol. Chem. 274, 5573-5580. 

Clusters or molecularities models trying to reproduce the correlation (27) are useful tools for gaining insight into the bonding of the oxide. 

---