Molecular drug designs

The interpretation of molecular surfaces is particularly important wherever molecular interactions, reactions, and properties play a dominant role, such as in drug design or in docking c.xpcrimcnts. 

The molecular surface of receptor site regions cannot be derived from the structure infoi mation of the molecule, bth represents the form ofthe active site of a protein surrounded by a ligand. This surface representation is employed in drug design in order to illustrate the volume of the pocket region or the molecular interaction layers [186. ... 

Dean P M (Editor) 1995. Molecular Similarity in Drug Design. London, Blackie Academic and Professional. 

Marshall G R 1955. Molecular Modeling in Drug Design. In Wolff M E (Editor) Burger s Medicinal Chemistry and Drug Discovery. 5th Edition, Volume 1. New York, John Wiley Sons, pp. 573-659. 

History and Objectives of Quantitative Drug Design. In Hansch C, P G Sammes and J B lor (Editors) Comprehensive Medicinal Chemistry Volume 4. Oxford, Pergamon Press, pp. 1-31. emd H van de 1995. Chemometric Methods in Molecular Design. Weinheim, VCH Publishers. 

Pearlman R S and K M Smith 1998. Novel Software Tools for Chemical Diversity. Perspectives in Dn Discovery and Design vols 9/10/ll(3D QSAR in Drug Design Ligand/Protein Interactions ar Molecular Similarity), pp. 339-353. 

C W 1979. Isosterism and Molecular Modification in Drug Design. Chemical Society Reviews 53-580. 

There are now extensive databases of molecular structures and properties. There are some research efforts, such as drug design, in which it is desirable to hnd all molecules that are very similai to a molecule which has the desired property. Thus, there are now techniques for searching large databases of structures to hnd compounds with the highest molecular similarity. This results in hnding a collection of known structures that are most similar to a specihc compound. 

A. R. Leach, Molecular Modelling Principles and Applications Longman, Essex (1996). G. A. Jeffrey, J. F. Piniela, The Application of Charge Density Research to Chemistry and Drug Design Plenum, New York (1991). 

Guidebook on Molecular Modeling in Drug Design N. C. Cohen, Ed., Academic, San Diego (1996). 

Molecular Modelling and Drug Design J. G. Vintner, M. Gardner, Eds., CRC, Boca Raton (1994). 

A. Itai, Y. Mizutani, Y. Nishibata, and N. Tomioka, in N. C. Cohen, Guidebook on Molecular Modeling in Drug Design, Academic Press, San Diego, Calif., 1996, pp. 93-138. 

M. S. Tute, in C. A. Ramsden, vol. ed.. Comprehensive Medicinal Chemisty, Vol. A, Quantitative Drug Design, Pergamon Press, New York, 1990, pp. 1—32. Definition of Molecular Modeling and Uses of CAMM ... 

Molecular recognition of protein-ligand complexes and drug design 97CRV1369. 

Dean, P. M. (ed.). Molecular similarity in Drug Design, Glasgow Blackie Academic and Professional, Chapman Hall, 1995. 

Korolkovas, A. Essentials of Molecular Pharmacology — Background for Drug Design, Chapter 4, New York, Wiley 1970... 

The increased speed of structure determination necessary for the structural genomics projects makes an independent validation of the structures (by comparison to expected properties) particularly important. Structure validation helps to correct obvious errors (e.g. in the covalent structure) and leads to a more standardised representation of structural data, e.g. by agreeing on a common atom name nomenclature. The knowledge of the structure quality is a prerequisite for further use of the structure, e.g. in molecular modelling or drug design. 

In general the relevance of predictions of structure-function relationships based on molecular modeling and structural bioinformatics are threefold. First they can be used to answer the question of which partners (proteins) could interact. Second, predictions generate new hypotheses about binding site, about molecular mechanisms of activation and interaction between two partners, and can lead to new ideas for pharmacological intervention. The third aim is to use the predictions for structure-based drug design. 

Common to all three aims is that silico-derived predictions can rationalize experimental efforts either by well-directed very specific molecular biological experiments like site directed mutations or e.g., by reducing the number of compounds to screen experimentally for drug design. 

Understanding the relationship between molecular structure and materials piroperties or biological activity is one of the most important facets of biomaterials synthesis and new-drug design. This is especially true for polyphosphazenes, where the molecular structure and properties can be varied so widely by small modifications to the substitutive method of synthesis. 

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