What simulation output, related to flexibility and complex stability over time, helps identify unwanted ligand flapping in drug candidates?
Answer
RMSF
RMSF, or Root Mean Square Fluctuation, is a metric derived from analyzing the time evolution of the MD trajectory. It specifically measures the deviation or flexibility of individual atoms or residues within the protein complex over the simulation duration. High RMSF values pinpoint regions of high flexibility or instability. In the context of lead optimization, monitoring the RMSF of the ligand helps researchers detect 'ligand flapping,' where the drug candidate moves erratically or loses critical contacts repeatedly throughout the simulation, signaling potential instability even if the initial fit score was promising.
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