ArticlePharmaceutical research1998
Predicting drug absorption from molecular surface properties based on molecular dynamics simulations.
Article in Pharmaceutical research, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Antibacterial Properties and Computational Insights of Potent Novel Linezolid-Based Oxazolidinones.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Molecular dynamics of fibric acids.European journal of chemistry (Print) · 2022Article
- Simulation Models for Prediction of Bioavailability of Medicinal Drugs-the Interface Between Experiment and Computation.AAPS PharmSciTech · 2022Review
- Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations.The AAPS journal · 2017Review
- Drug discovery and regulatory considerations for improving in silico and in vitro predictions that use Caco-2 as a surrogate for human intestinal permeability measurements.The AAPS journal · 2013Article
- Physiologically based pharmacokinetic models: integration of in silico approaches with micro cell culture analogues.Current drug metabolism · 2012Review
- Testing physical models of passive membrane permeation.Journal of chemical information and modeling · 2012Article
- Retronasal odor representations in the dorsal olfactory bulb of rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Predicting and improving the membrane permeability of peptidic small molecules.Journal of medicinal chemistry · 2012Article
- Biomolecular chemistry of isopropyl fibrates.Journal of pharmaceutical sciences · 2012Article
- Quantum mechanical polar surface area.Journal of computer-aided molecular design · 2012Article
- Intestinal lymphatic transport for drug delivery.Advanced drug delivery reviews · 2011Review
- Modeling kinetics of subcellular disposition of chemicals.Chemical reviews · 2009Review
- An atomistic model of passive membrane permeability: application to a series of FDA approved drugs.Journal of computer-aided molecular design · 2007Article
- Computational approaches for modeling human intestinal absorption and permeability.Journal of molecular modeling · 2006Article
- Theoretical predictions of drug absorption in drug discovery and development.Clinical pharmacokinetics · 2002Review
- Chemical substituent effect on pyridine permeability and mechanistic insight from computational molecular descriptors.Molecular pharmaceuticsArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo develop an efficient method for generating representative conformations for calculation of the conformationally dependent molecular surface area, and to investigate the relation between this parameter and the permeability in Caco-2 cells.
methodsHigh temperature molecular dynamics (MD) simulations were used to obtain 1000 conformations of six beta-blocking agents and their prodrugs. The Boltzmann averaged (B.a.) polar surface area of the 1000 conformations was correlated to the apparent permeability coefficients (Papp) for transport across filter-grown Caco-2 cells.
resultsSampling of 1000 conformations during the MD simulations was sufficient for obtaining a representative set of conformations. The B.a. polar water accessible surface area (PWASA) yielded an excellent linear correlation with Papp for both series of compounds under study (R2 = 0.98). Thus, the improved permeability of the prodrugs could be explained by a reduced PWASA. The improvement of permeability after derivatization correlated positively with the size of the non-polar water accessible surface area-suggesting a synergistic effect of the cyclopropyl and the non-polar parts of the molecule to shield the polar parts from contact with water.
conclusionsAn efficient method for generating the representative conformations for calculation of the B.a. polar surface area has been established. An excellent linear correlation explaining the improved permeability of the prodrugs was obtained.
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9688046What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.