Life Sciences & Biotechnology
Title : | Computational approach to investigate the molecular mechanism of arsenic and drug transport in human, plant and parasitic aquaglyceroporin channels |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Ramasubbu Sankararamakrishnan, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | rsankar@iitk.ac.in |
Equipments : | UPS
High Performance Computing Servers |
Details
Executive Summary : | Membrane proteins, including channel proteins like potassium, sodium, calcium, chloride channels, and aquaporins, are present in nearly 30% of the human proteome and play a crucial role in various physiological processes. Aquaporins, part of the Major Intrinsic Proteins (MIPs) superfamily, are water transporting and glycerol-specific. They have a unique helical hour-glass fold with six transmembrane helices and two half-helices. MIPs have highly conserved Asn-Pro-Ala motifs at the N- and C-terminal halves. There are 13 MIP homologs in humans, while plants have 30 to 70 MIPs. Many human diseases are caused by defects in the function of human aquaporins, and small molecule blockers of aquaporin channels offer significant therapeutic opportunities. However, understanding the arsenic uptake mechanism at molecular level in humans and plants is an important problem. This knowledge will provide strategies to prevent arsenic uptake in aquaporins in humans and plants. An unconventional aquaglyceroporin in Trypanosoma brucei (TbAQP2) has been implicated in the fatal human disease sleeping sickness. Experimental studies suggest that TbAQP2 may transport pentamidine and melarsoprol, which is increasingly important due to drug resistance. This proposal proposes using computational approaches to understand the transport mechanism of arsenic species in human aquaporins and the drug uptake of pentamidine/melarsoprol in TbAQP2. Variations in all 13 aquaporin genes will be analyzed in the context of arsenic transport, with a particular focus on variations in the Indian population. |
Total Budget (INR): | 35,16,260 |
Organizations involved