Structural and Functional Study of Folate Transporters by Computational Approach

Abstract

Folate transport is crucial for proper proliferation of cells. Amongst humans the folate is newlineprocured from external sources since it is not synthesized in the human body. Hence specific newlinetransporters are involved in uptake of folate. For the malignant cancerous cells these folates are newlinecrucially required on very frequent rate to fulfill the rapid proliferation of the cancerous cells. newlineIn the present study we have comparatively studied different proton pump inhibitory antagonist newlinedrug molecules which could be a potential candidate to inhibit the folate uptake by the human newlineProton Coupled Folate Transporter (hPCFT). These candidate antagonists include 27 most newlineprominent drug molecules. Out of these antagonist drugs, the Leucovorin and Nolatrexed newlinemolecules were observed to be specifically bind to the key active site loop (G155XXG158) of the newlinehPCFT transporter. The Binding energy of the Leucovorin and Nolatrexed was also newlinecomparatively found lowest -7.5 and -7.6 kcal/mol respectively. This present study clearly newlinesuggested that the human Proton Coupled Folate Transporter (hPCFT) interaction with newlineLeucovorin and Nolatrexed are more effective than other antagonists. Hence, we concluded from newlinethis study that Leucovorin and Nolatrexed antagonist drugs are the most potential inhibitory newlinecandidates for folate transport. The Human Proton Folate Transporter could be an important newlinetarget for specific treatment for future drug discovery and therapeutic development. newline