RESUMEN
Silk continues to amaze: over the past decade, new research threads have emerged that include the use of silk fibroin for advanced pharmaceutics, including its suitability for drug delivery. Despite this ongoing interest, the details of silk fibroin structures and their subsequent drug interactions at the molecular level remain elusive, primarily because of the difficulties encountered in modeling the silk fibroin molecule. Here, we generated an atomistic silk model containing amorphous and crystalline regions. We then exploited advanced well-tempered metadynamics simulations to generate molecular conformations that we subsequently exposed to classical molecular dynamics simulations to monitor both drug binding and release. Overall, this study demonstrated the importance of the silk fibroin primary sequence, electrostatic interactions, hydrogen bonding, and higher-order conformation in the processes of drug binding and release.
Asunto(s)
Doxorrubicina/química , Portadores de Fármacos/química , Fibroínas/química , Animales , Bombyx/química , Cristalización , Liberación de Fármacos , Enlace de Hidrógeno , Simulación de Dinámica Molecular , Conformación Proteica , Electricidad Estática , Termodinámica , Agua/químicaRESUMEN
Reported here is a rational approach for the selection of solvents intended for use in physical form screening based on a novel chemoinformatics analysis of solvent properties. A comprehensive assessment of eight clustering methods was carried out on a series of 94 solvents described by calculated molecular descriptors using the clusterSim package in R. The effectiveness of clustering methods was evaluated using a range of statistical measures as well as increasing efficiency of solid form discovery using a cluster-based solvent selection approach. Multidimensional scaling was used to illustrate cluster analysis on a two-dimensional solvent map. The map presented here is a valuable tool to aid efficient solvent selection in physical form screens. This tool is equally applicable to any scientific area which requires a solubility dependent decision on solvent choice.
Asunto(s)
Informática/métodos , Bibliotecas de Moléculas Pequeñas/química , Solventes/química , Modelos Moleculares , Conformación MolecularRESUMEN
This paper provides a viable, reproducible and robust method for immobilising hydroxyl tethered iridium-rhodium complexes. The materials have been shown to be both effective and recyclable in the process of catalytic transfer hydrogenation with minimal metal leaching.
