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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. March 2005, Volume 4, Number 3, 194-209 |
New Application Design for a 3D Hydropathic Map-Based Search for
Potential Water Molecules Bridging between Protein and Ligand
Glen E. Kellogg, Micaela Fornabaio, Deliang L. Chen, and Donald J. Abraham
Internet Electron. J. Mol. Des. 2005, 4, 194-209
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Abstract:
The design of an extension to the HINT (Hydropathic
INTeractions) program for locating and automatically placing in
relevant orientations bridging water molecules is described in
detail. This application is used to analyze the structures of HIV-1
protease-inhibitor complexes for five key bridging water
molecules. The tool locates the water molecules with an overall
accuracy of 1.28 ± 0.55 Å, and orients them (relative to
potentially erroneous molecular mechanics optimized water
molecules) to 41 ± 23 degrees. This automated placement is in
contrast to other programs that calculate 3D contour maps of
energetically-likely binding locations for water molecules, which
must be followed by manual placement and energy minimization
of these water positions and orientations to create the model.
Also, the new object-oriented toolkit design for the HINT
program (http://www.edusoft-lc.com/toolkits/) is described. The
toolkit includes molecule, atom and monomer objects to
represent chemical structure. A second class of objects describes
3D maps and includes tools for their manipulation. The hint
objects are designed around the primary goals of HINT:
partitioning (calculating LogPo/w for) molecules, calculating
interaction scores between molecules and calculating 3D maps of
molecular and intermolecular hydropathy.
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