Molecular modelling study

Monte Carlo (MC) techniques for molecular simulations have a long and rich history, and have been used to a great extent in studying the chemical physics of polymers. The majority of molecular modeling studies today do not involve the use of MC methods however, the sampling capabiUty provided by MC methods has gained some popularity among computational chemists as a result of various studies (95—97). Relevant concepts of MC are summarized herein. 

The hst which follows gives an outline of the properties of a Monte Carlo simulation used in the context of molecular modeling studies for sampling either multiple conformations of smaller, flexible stmctures or multiple local minima of larger macromolecules or polymers ... 

The molecular modeling studies with this set of dopaminergic ligands involved the following analytical steps ... 

Figure 3 The chemical structures of the ligands used in the molecular modeling study of the Di dopamine receptor. The ligands were divided into two groups (active and inactive) based on their pharmacological properties. The hypothesized pharmacophoric elements are shown in bold.

All molecular modeling studies were performed with the multifaceted molecular modeling software package SYBYL (Tripos Associates Inc., St. Louis, MO). 

QSAR and Molecular Modeling Studies in Heterocyclic Drugs II... 

Importantly, there was a general marked selectivity for inhibition of influenza A over influenza B viral sialidases in the carboxamide series (e.g. as seen with 27) (Smith et al. 1996, 1998), determined from crystallographic and molecular modelling studies (Smith et al. 1996 Taylor et al. 1998) to be due to the relative abilities of each of the sialidases to absorb the structural changes required to accommodate the hydrophobic alkyl chains in the glycerol side-chain binding pocket. In influenza... 

Taylor NR, von Itzstein M (1994) Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. J Med Chem 37 616-624... 

Taylor NR, Cleasby A, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethel R, Colman P, Varghese J (1998) Dihydropyrancarboxamides related to zanamivir a new series of inhibitors of influenza virus sialidases. Crystallographic and molecular modeling study of complexes of 4-amino-4//-pyran-6-carboxamides and sialidase from influenza virus types A and B. J Med Chem 41 798-807... 

Geldenhuys WJ, Lockman PR, McAfee JH, Fitzpatrick KT, Van der Schyf CJ and Allen DD. Molecular modeling studies on the active binding site of the blood-brain barrier choline transporter. Bioorg Med Chem Lett 2004 14 3085-92. 

In recent years it has been realized that molecular modeling studies of the alkaloidal molecules having different pharmacological activities are highly important in order to explain their mechanisms, at least partially in some cases. This chapter presents and critically reviews some examples of molecular modeling studies of alkaloids, based on their different biological properties or sometimes performed in parallel to explain their biochemical effects. 

Gambari R, Lampronti I, Bianchi N, Zuccato C, Viola G, Vedaldi D, Dall Acqua F (2007) Structure and Biological Activity of Furocoumarins. 9 265-276 Garg R, Bhhatarai B (2006) QSAR and Molecular Modeling Studies of HIV Protease Inhibitors. 3 181-272... 

Hadjipavlou-Litina D (2006) QSAR and Molecular Modeling Studies of Factor Xa and Thrombin Inhibitors. 4 1-53... 

Researchers at Combio and Arpida have reported a series of isoxazole-3-hydroxamic acids as PDF inhibitors [109], Molecular modelling studies predict that the aryl substituent of isoxazole (37) binds into the SF pocket and that the oxygen atom of the isoxazole is involved in a H-bonding interaction with Ile-44 in E. coli PDF, similar to the PF carbonyl of actinonin. None of the inhibitors reported has sub-micromolar inhibitory activity against E. coli or S. aureus PDF. Not surprisingly, these moderately active inhibitors also lack antibacterial activity. 

Comba et al. reported structural properties (in the solid state and in solution) and molecular modeling studies on a dicopper(II) complex (545) (SP) of a macrocyclic amide ligand.443 In 1993... 

In a combined MALDI-ToF MS, ion mobility experiment and molecular modelling study, Baker and co-workers [120] studied the sequencing in copolymers of glycidyl methacrylate and butyl methacrylate, Figure 20, with different termination groups. 

Molecular modeling studies revealed a similar binding mode for (5)-2-nitro-1 -phenylethanol in the catalytic center of ///)HNL as was determined experimentally for (5)-mandelonitrile, preserving all mechanistically important polar interactions with active-site residues. This implies that the mechanism for the cyanohydrin reaction applies to the nitroaldol reaction as well. 

Cundari, T.R., Dinescu, A., Zhu, D. andHua, L. (2007) A molecular modeling study on the enantioselectivity of aryl alkyl ketone reductions by a NADPH-dependent carbonyl reductase. Journal of Molecular Modeling, 13 (6-7), 685-690. 

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