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Evaluation of a method for controlling molecular scaffold diversity in de novo ligand design
TLDR
We describe an algorithm for the automated generation of molecular structures subject to geometric and connectivity constraints. Expand
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Receptor flexibility in de novo ligand design and docking.
One of the major problems in computational drug design is incorporation of the intrinsic flexibility of protein binding sites. This is particularly crucial in ligand binding events, when induced fitExpand
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A validation study on the practical use of automated de novo design
TLDR
The de novo design program Skelgen has been used to design inhibitor structures for four targets of pharmaceutical interest. The designed structures are compared to modeled binding modes of known inhibitors (i) visually and (ii) by means of a novel similarity measure. Expand
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Assessment of multiple binding modes in ligand-protein docking.
Computational ligand-protein docking is routinely used for binding mode prediction. We have quantified the effect of considering multiple docking solutions on the success rate of obtaining theExpand
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A branch-and-bound method for optimal atom-type assignment in de novo ligand design
TLDR
This paper investigates a computational procedure for the determination of the atom types on the vertices of a molecular skeleton to optimize interaction with the receptor site whilst maintaining a synthetically reasonable structure. Expand
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The effect of tightly bound water molecules on the structural interpretation of ligand-derived pharmacophore models
TLDR
The importance of the consideration of water molecules in the structural interpretation of ligand-derived pharmacophore models is explored. Expand
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Receptor flexibility in the in silico screening of reagents in the S1' pocket of human collagenase.
A major difficulty in structure-based molecular design is the prediction of the structure of the protein-ligand complex because of the enormous number of degrees of freedom. Commonly, the targetExpand
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A new quantum stochastic tunnelling optimisation method for protein–ligand docking
Abstract A novel hybrid optimisation method, called quantum stochastic tunnelling, is introduced. This method combines path integral Monte Carlo and stochastic tunnelling approaches. We haveExpand
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Scaffold hopping in de novo design. Ligand generation in the absence of receptor information.
We report here the de novo generation of chemotypes and scaffolds for the estrogen receptor, without use of the receptor structure in the assembly phase. Through use of ligand superpositions or aExpand
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De novo drug design: integration of structure-based and ligand-based methods.
Structure-based and ligand-based methods are used to derive predictive models in de novo drug design. Structure-based methods rely exclusively on prior knowledge of a protein structure to deriveExpand
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