MM-PBSA and the Importance of the Dielectric Constant for Kinase Drug Design

09 December 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Predicting the interactions between a set of small molecules and its target plays a critical role in drug discovery and development. Especially in later stages of the drug design process, when a reduced set of molecules is in focus, reliable and accurate binding affinity estimations are important for targeted modifications of given lead molecules.
Current limitations in affinity prediction originate from the lack of accurate estimates for solvation energy and entropy. MM-PBSA and the related MM-GBSA aim at providing better estimates.
From our studies we infer that the common approach using one dielectric constant for the binding pocket may be misleading (here in the case of a kinase), especially when designed ligands/drugs contain charges. Thus, a range of selected values for the solute dielectric constant is preferred for better and more reliable comparisons.


MM-PBSA, molecular mechanics Poisson Boltzmann surface area
drug design
dielectric constant


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