Chapter 5. Computational Modeling of Active Transporters
Synopsis
Author
Dr. Mudita Mishra
Associate Professor, Department of Phamacy (QSHS), Quantum University, Roorkee, Uttarakhand, India
Abstract
Computational modeling of active transporters involves advanced algorithms and mathematical techniques to predict drug-transporter interactions and transport mechanisms across biological membranes. These models integrate structural biology, physicochemical properties, and kinetic parameters to simulate the behavior of key transport proteins including P-glycoprotein, BCRP, nucleoside transporters, and peptide transporters. P-glycoprotein models predict drug efflux patterns and substrate recognition, while BCRP simulations assess drug resistance mechanisms. Nucleoside transporter models calculate concentration-dependent transport kinetics and competitive inhibition effects. Human peptide transporter (hPEPT1) algorithms determine peptide-like drug absorption rates and substrate specificity patterns. ASBT models compute bile acid transport mechanisms and drug interactions in the intestinal environment. Blood-brain barrier transport models specifically address the unique challenges of drug penetration into the central nervous system, considering factors like molecular flexibility and hydrogen bonding capacity. These computational approaches have significantly improved drug development efficiency by enabling early prediction of transport behavior, reducing the need for extensive experimental testing.
Keywords: Active transport modelling; P-glycoprotein; BCRP transporters; Nucleoside transport; Peptide transporters; ASBT modelling; OCT/OATP systems; BBB transport; Molecular dynamics
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