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Molecular mechanics force fields are widely used in computer-aided drug design for the study of drug candidates interacting with biological systems. In these simulations, the biological part is typically represented by a specialized biomolecular force field, while the drug is represented by a matching general (organic) force field. In order to apply these(More)
The applicability of a computational method, Site Identification by Ligand Competitive Saturation (SILCS), to identify regions on a protein surface with which different types of functional groups on low-molecular weight inhibitors interact is demonstrated. The method involves molecular dynamics (MD) simulations of a protein in an aqueous solution of(More)
Database screening using receptor-based pharmacophores is a computer-aided drug design technique that uses the structure of the target molecule (i.e. protein) to identify novel ligands that may bind to the target. Typically receptor-based pharmacophore modeling methods only consider a single or limited number of receptor conformations and map out the(More)
The site identification by ligand competitive saturation (SILCS) method identifies the location and approximate affinities of small molecular fragments on a target macromolecular surface by performing molecular dynamics (MD) simulations of the target in an aqueous solution of small molecules representative of different chemical functional groups. In this(More)
In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: Using the experimental structures of Aβ amyloid fibrils and all-atom molecular(More)
Solute sampling of explicit bulk-phase aqueous environments in grand canonical (GC) ensemble simulations suffer from poor convergence due to low insertion probabilities of the solutes. To address this, we developed an iterative procedure involving Grand Canonical-like Monte Carlo (GCMC) and molecular dynamics (MD) simulations. Each iteration involves GCMC(More)
Adequate bioavailability is one of the essential properties for an orally administered drug. Lipinski and others have formulated simplified rules in which compounds that satisfy selected physiochemical properties, for example, molecular weight (MW) ≤ 500 or the logarithm of the octanol-water partition coefficient, log P(o/w) < 5, are anticipated to likely(More)
Receptor-based pharmacophore modeling is an efficient computer-aided drug design technique that uses the structure of the target protein to identify novel leads. However, most methods consider protein flexibility and desolvation effects in a very approximate way, which may limit their use in practice. The Site-Identification by Ligand Competitive Saturation(More)
Occluded ligand-binding pockets (LBP) such as those found in nuclear receptors (NR) and G-protein coupled receptors (GPCR) represent a significant opportunity and challenge for computer-aided drug design. To determine free energies maps of functional groups of these LBPs, a Grand-Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) strategy is combined with(More)