Molecular Modeling of Aquaporins from .

Aquaporins are membrane proteins responsible for permeating water, ions, dissolved gases, and other small molecular weight compounds through the protective cell membranes of living organisms. These proteins have been gaining increased importance as targets for treating a variety of parasitic diseases, since they control key physiological processes in the life cycle of parasitic protozoans, such as the uptake of nutrients, release of metabolites, and alleviation of osmotic stress. In this work, we use homology modeling to build three-dimensional structures for the four main aquaporins encoded and expressed by , a protozoan that causes leishmaniasis and affects millions of people worldwide. Physico-chemical properties of the proposed models for LmAQP1, LmAQPα, LmAQPβ, and LmAQPγ are then investigated using molecular dynamics simulations and the reference interaction site model (RISM) molecular theory of solvation. Pore characteristics, water permeation, and potential of mean force across the AQP channels for water, methanol, urea, ammonia, and carbon dioxide are examined and compared with results obtained for a protozoan () aquaporin for which a crystal structure is available.