To realize computational “de novo” drug design, we propose a procedure of the combination of affinity evaluation and binding structure search as follows: (i) well-tempered metadynamics for exploring the available binding structures of new drug-like molecule to a target, (ii) the conversion from collective variables to the initial coordinate values for restraining potentials by reweighting method, and (iii) the execution of the alchemical free energy calculations for each binding pose.<br/>We have applied this approach to the computation of the binding affinity including multiple ligand poses in theophylline/RNA aptamer complex.

Accurate estimate of ligand-binding affinity using alchemical free energy calculation via metadynamics

253rd National Meeting (2017)

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