MDCKpred calculates MDCK permeability coefficient of small molecule based on regression model developed using membrane-interaction chemical features. Structure-based modeling to understand transport of small molecules through biological membrane can be developed by enumerating the intermolecular interactions of small molecule with a biological membrane, usually a dimyristoylphosphatidylcholine (DMPC) monolayer. This ADME (absorption, distribution, metabolism and excretion) property based on Madin-Darby Canine Kidney (MDCK) cell lines demonstrates intestinal drug absorption of small molecules and correlated to Human intestinal absorption which acts as a determining factor to forecast small molecule prioritization in drug discovery projects. The web tool allows users to calculate the MDCK permeability coefficient (nm/s) instantly by providing simple inputs. The chemical-interaction features representing the intermolecular contacts of small molecule when passively diffused through the phospholipid-rich biological membrane are taken from different parts of the DMPC molecule viz. head, middle and tail regions and hence accounts the overall intermolecular contacts of small molecule (solute) within the DMPC monolayer.
INPUTS FOR MODELING MDCK PERMEABILITY COEFFICIENT:
1. Number of Nitrogen atoms present in the small molecule.
2. Number of Oxygen atoms present in the small molecule.
3. Ipc descriptor: A descriptor based on polynomial coefficients using information theory.
Patel RD, Kumar SP, Pandya HA and Solanki HA (2018). MDCKpred: A web tool to calculate MDCK permeability coefficient of small molecule using membrane-interaction chemical features. Toxicology Mechanisms and Methods, doi: 10.1080/15376516.2018.1499840. Link to article: https://www.tandfonline.com/doi/abs/10.1080/15376516.2018.1499840
WEB TOOL DEVELOPED BY
Rikin D. Patel, Sivakumar Prasanth Kumar, Himanshu A. Pandya and Hitesh A. Solanki
Department of Bioinformatics, Gujarat University