Computer-aided molecular modelling

Bearing, A., Computer-aided Molecular Modelling Research Study or Research Tool... 

Few scientists have had an impact on their chosen research field as much as Peter Kollman on computer-aided molecular modeling and its application to problems in both chemistry and biology. Sadly, Peter died in May leaving behind many friends and scientific collaborators from around the world. 

For Trichoderma reesei the cellulases most thoroughly investigated with respect to their structural properties are CBH I and CBH II and to a lesser extent the two en-doglucanases (EG I and EG III) 11 (Table I). For most other cellulases structural characterizations are confined to the amino add sequence as deduced from the base sequence of the respective genes and to sequence related investigations such as hydro-phobic cluster analysis 10 or computer aided molecular modelling and homology... 

Molecular design has enjoyed a long history, from the preliminary trial-and-error stage to the contemporary computer-aided molecular modeling stage. In this chapter, the latter, in silico design, for nuclear applications is focused on and reviewed. 

The molecular structure of polysaccharides from Klebsiella serotype K8 has been examined by X-ray diffraction and computer-aided molecular modeling. The most favorable molecular model was not the one which had the maximum number of intra-molecular hydrogen bonds. This result suggests that in the analysis one should not a priori choose the molecular model which has the largest number of intra-molecular hydrogen bonds. 

E. Weber, Computer-Aided Molecular Modeling Alternatives to Animal Research, in Monographien des Forschungszentrums Juelich, 6, Forschungszentrum Juelich, Juelich, Germany, 1991. 

Mahmoudian, M. The cannabinoid receptor Computer-aided molecular modelling and docking of ligand. J. Mol. Graphics Mod., 1997, 15, 149-153. 

Mahmoudian, M. The complex of human Gs protein with Ps-adrenergic receptor A computer-aided molecular modelling study. J. Mol. Graph., 1994, 12,22-34. 

Based on the expertise from toxicology and/or prediction of biotransformation products by computer-aided molecular modelling, an educated guess can be made on possible metabolites of a particular parent drag. This information can be apphed for the synthesis and a target-oriented detection strategy. 

Molecular ModeUng = Computer-Aided Molecular Modeling drug design... 

The data (Table 8 and Scheme 3) illustrate again the possible length selectivity, with a maximum affinity for (gly)3 with receptor 21, and for (gly>4 with receptor 22, in accordance with computer-aided molecular modeling (see also our website). Host 21 shows a pronounced sequence selectivity for aromatic amino acids in position 1 of the tripeptides which as in the case of receptor 15 systematically decreases for aliphatic amino acids with in the order val>leu>ile>ala>gly. Notably, proline in position 1 leads to particular affinity drop, likely due to geometric mismatch. A preference for aromatic amino acids in position 1 is observed also with host 22, more pronounced with trp than with phe. In methanol, large constants of nearly lO M are found, but the sequence selectivity disappears almost entirely (see Table 8) this highlights the importance of hydrophobic side-chain interactions that are also visible in computer simulated structures (see website). 

The benzylamino residue in 25 is immersed into the CD cavity prior to complexa-tion of the phenyl ring, as evident from NMR analyses. Complexation with a peptide then requires that this intramolecular association must be given up, which explains why the affinity is not increased by possible lipophilic interactions of aromatic peptide side chains and the benzyl group outside the cavity. The conformational switching triggered by complexation with a peptide was followed by suitable NMR experiments, and is supported by computer-aided molecular modeling (see our website). 

Ghose A, Crippen G, Revankar G, McKeman P, Smee D, Robbins R. Analysis of the in vitro activity of certain ribonucleosides against parainfluenza virus using a novel computer-aided molecular modeling procedure. J Med Chem 1989 32 746-756. 

A. Dearing, ]. Comput.-Aided Mol. Design, 2, 179 (1988). Computer-Aided Molecular Modelling Research Study or Research Tool. ... 

An enormous amount of eoneerted research particularly related to fundamental aspeets of drug design, synthesis, conformational energy studies, and computer-aided molecular modelling (CAMM)... 

A. Ghose, G. Crippen, G. R. Rcvankar, P. McKeman, D. Smee, and R. Robins, J. Med. Chem., 32,746 (1989). Analysis of the In Vitro Activity of Certain Ribonucleosides Against Parinfluenza Virus Using a Novel Computer-Aided Molecular Modeling Procedure. 

R. K. Gupta and A. K. Bhattachaijee, Discovery and Design of New Arthropod/Insect Repellents by Computer-Aided Molecular Modeling In Insect Repellents Principles, Methods, and Uses, Debboun, M. Frances, S. P. Strickman, D., Eds. CRC Press Boca Raton, FL, 2007 pp. 195-228. 

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