Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.11889/5436
Title: pMD-membrane : a method for ligand binding site identification in membrane-bound proteins
Authors: Prakash, Priyanka
Sayyed-Ahmad, Abdallah
Gorfe, Alemayehu A.
Issue Date: Oct-2015
Publisher: PLOS
Citation: 1. Prakash P, Sayyed-Ahmad A and Gorfe AA, "pMD-membrane: A method for ligand binding site identification in membrane-bound proteins.", PLoS computational biology 11(10): e1004469, 2015.
Abstract: Probe-based or mixed solvent molecular dynamics simulation is a useful approach for the identification and characterization of druggable sites in drug targets. However, thus far the method has been applied only to soluble proteins. A major reason for this is the potential effect of the probe molecules on membrane structure. We have developed a technique to overcome this limitation that entails modification of force field parameters to reduce a few pairwise non-bonded interactions between selected atoms of the probe molecules and bilayer lipids. We used the resulting technique, termed pMD-membrane, to identify allosteric ligand binding sites on the G12D and G13D oncogenic mutants of the K-Ras protein bound to a negatively charged lipid bilayer. In addition, we show that differences in probe occupancy can be used to quantify changes in the accessibility of druggable sites due to conformational changes induced by membrane binding or mutation.
URI: http://hdl.handle.net/20.500.11889/5436
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