Insights into Opiate Binding and Activation of μ-Opioid Receptors -- Amir Barati Farimani скачать в хорошем качестве

Insights into Opiate Binding and Activation of μ-Opioid Receptors -- Amir Barati Farimani

Many important analgesics relieve pain in human through binding to μ-Opioid receptors (μOR). To design effective pain medications, we should gain a deep understanding of the activation mechanism of μOR and how they attract drugs to bind. Since the nature of conformational changes in the activation pathway of these receptors is very subtle and encompass microsecond timescales, we took advantage of Blue Waters to run thousands of MD simulations to be able to shed light into drug-receptor interaction. We used Markov State Models and machine learning techniques to characterize the conformational changes induced by ligand. Time-Structure Based Independent Component Analysis enabled us to find and pick the most significant reaction coordinates and their associated trajectories among the massive number of trajectories produced by Blue Waters. We found significant intermediates in the binding pathway of ligand and activation of the receptor.