Characterizing Functional Motions and Molecular Mechanisms of Sugar Transporters

Emad Tajkhorshid, University of Illinois at Urbana-Champaign

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Emad Tajkhorshid, Po-Chao Wen, Jing Li, Paween Mahinthichaichan, Joshua Vermaas, Javier Baylon, Christopher Mayne, Yuhang Wang, Mrinal Shekhar, Sundarapandian Thangapandian, Noah Trebesch, Melanie Muller, Latifeh Navidpour, Tao Jiang, Zhiyu Zhao, Eric Shinn, Ahmad Raeisi Najafi

The goal of the proposed simulations is to study functionally relevant, large-scale structural transitions in sugar (trans)porters. They play a fundamental role in distribution of sugar molecules, and are therefore of high relevance to human physiology and disease. Description of large-scale protein structural changes at high resolutions requires sampling high-dimensional free energy landscapes that are inaccessible to conventional simulation techniques such as regular molecular dynamics (MD) simulations. We have developed and tested a novel computational approach that, while numerically expensive, has been the most effective way to describe large-scale structural transitions using non-equilibrium methods employing system-specific collective variables, and a novel combination of several state-of-the-art sampling techniques. The approach is based on loosely coupled, multiple-copy MD simulations of large macromolecular systems, which require massive computing resources; hence this project is only possible on platforms such as Blue Waters.