pMD-Membrane: A Method for Ligand Binding Site Identification in Membrane-Bound Proteins

摘要: 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 method has been applied only to soluble proteins. A major reason this potential effect probe molecules on membrane structure. We have developed technique overcome limitation that entails modification force field parameters reduce few pairwise non-bonded interactions between selected atoms bilayer lipids. used resulting technique, termed pMD-membrane, identify allosteric ligand binding G12D G13D oncogenic mutants K-Ras protein bound negatively charged lipid bilayer. In addition, we show differences occupancy can be quantify changes accessibility due conformational induced by mutation.