Drug molecular interaction field

Goodford, P. J. The basic principles of GRID. In Molecular Interaction Fields Application in Drug Discovery and ADME Prediction (Methods and Principles in Medicinal Chemistry), Cruciani, G., Mannhold, R. Kubinyi, H., Folkers, G. 

Goodford P (2006) In Cruciani G, Mannhold R, Kubinyi H, Folkers G (eds) Molecular interaction fields applications in drug discovery and ADME prediction. Wiley, New York, p 3... 

The interaction of drug molecules with biological membranes is a three-dimensional (3D) recognition that is mediated by surface properties such as shape, Van der Waals forces, electrostatics, hydrogen bonding, and hydrophobicity. Therefore, the GRID force field [5-7], which is able to calculate energetically favorable interaction sites around a molecule, was selected to produce 3D molecular interaction fields. 

Wolohan P.R.N. Clark R.D. Predicting drug pharmacokinetic properties using molecular interaction fields and SIMCA. Journal of Computer-Aided Molecular Design, 2003, 17 (1), 65-76. 

The set of 51 benzamidine-based thrombin inhibitors was taken from the study of Sugano et al. (2000). Experimental rat everted sac permeabilities were expressed as log(ES A) values.2 The experimental permeability in this assay is expressed as ratio of outer (mucosal side) concentration of the drug and inner (serosal side) concentration after 1 h incubation of the everted sac of rat small intestine. All molecules were treated in their neutral form and converted into their 3D structures using CORINA (Sadowski et al. 1992). From GRID molecular interaction fields for water, dry, and carbonyl oxygen probes, a set of 72 VolSurf descriptors (Cruciani et al. 2000) was computed and analysed as described above. 

R. C.Wade, Molecular Interaction Fields, in 3D QSAR in Drug Design. Theory, Methods and Applications, H. Kubrnyi (ed.) ESCOM, Leiden, 1993, pp. 486-505. 

Molecules are complex entities that can be numerically described in many different ways. The molecular interaction fields (MIF) represent a very particular molecular property the ability of a molecule to establish energetically favorable interactions with other molecules. For this reason, MIF have been widely used in the field of drug discovery and development, since most biological properties of a compound depend on its ability to bind different kinds of biomolecules, such as transporters, receptors and enzymes. 

My scientific career was guided and complemented by these scientists, and the reasons why my interests are so sparse depend on their enthusiasm and imprinting. However, one thing I have always used in all the problems I have encountered, or in all the procedure I developed. I have always used Molecular Interaction fields to describe the structures of chemical and biological systems. After so may years of work, I m still fascinated by the amount of information they contain. One never finishes to find new ways to extract information from them. Moreover, combining MIE with chemometric tools, is a powerful approach to all the fields of computer assisted drug development. 

Volume 27 of our series Methods and Principles in Medicinal Chemistry is dedicated to Molecular Interaction Fields and their impact on current drug research. 

Cruciani G. Molecular interaction fields. In Applications in Drug Discovery and ADME Prediction. Mannhold R, Kubinyi H, Folker G, eds. 2005. Wiley-VCH, Weinheim, Germany. 

Liljefors, T. (1998). Progress in Force-Field Calculations of Molecular Interaction Fields and Intermolecular Interactions. In 3D QSAR in Drug Design - Vol. 2 (Kubinyi, H., Folkers, G. and Martin, Y.C., eds.), Kluwer/ESCOM, Dordrecht (The Netherlands), pp. 3-17. 

Cruciani, G., Pastor, M., Benedetti, P. and Clementi, S. (2001a) From molecular interactions fields to a widely applicable set of descriptors, in Rational Approaches to Drug Design (eds H.-D. Hol e and W. Sippl), Prous Science, Barcelona, Spain, pp. 159-170. 

Liljefors, T. (1998) Progress in force-field calculations of molecular interaction fields and intermolecular interactions, in 3D QSAR in Drug Design, Vol. 2... 

In the third step (negative image sampling), the chemical features in the active site are known by molecular interaction field analysis and identification of excluded volumes [43]. It has its appheation in designing novel inhibitors in the drug discovery field [44],... 

Goodford P (2006) The basic principles of GRID. In Cruciani G (ed) Molecular interaction fields. Applications in drug discovery and ADME prediction. Methods and principles in medicinal chemistry, vol 27. Wiley-VCH, Weinheim, pp 3-26 Hoskuldsson A (1988) PLS regression methods. J Chemom 2(3) 211-228 Fradera X, Amat L, Besalu E, Carbo-Dorca R (1997) Application of molecular quantum similarity to QSAR. Quant Struct-Act Rel 16(l) 25-32... 

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