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Optimization of cutting schemes for the evaluation of molecular electrostatic potentials in proteins via Moving-Domain QM/MM

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Abstract

This work presents new developments of the moving-domain QM/MM (MoD-QM/MM) method for modeling protein electrostatic potentials. The underlying goal of the method is to map the electronic density of a specific protein configuration into a point-charge distribution. Important modifications of the general strategy of the MoD-QM/MM method involve new partitioning and fitting schemes and the incorporation of dynamic effects via a single-step free energy perturbation approach (FEP). Selection of moderately sized QM domains partitioned between \(C_\alpha \) and C (from C=O), with incorporation of delocalization of electrons over neighboring domains, results in a marked improvement of the calculated molecular electrostatic potential (MEP). More importantly, we show that the evaluation of the electrostatic potential can be carried out on a dynamic framework by evaluating the free energy difference between a non-polarized MEP and a polarized MEP. A simplified form of the potassium ion channel protein Gramicidin-A from Bacillus brevis is used as the model system for the calculation of MEP.

Schematic representation of the Moving Domain QM/MM method

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Acknowledgements

J.A.G acknowledges financial support from the Camille and Henry Dreyfus New Faculty Award, start-up package funds from University of Connecticut, and supercomputer time from the National Energy Research Scientific Computing (NERSC) Center.

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  1. Department of Chemistry, University of Connecticut, 55 North Eagleville Rd, Unit 3060, Storrs, CT, 06269, USA

    Lochana C. Menikarachchi & José A. Gascón

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  1. Lochana C. Menikarachchi
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  2. José A. Gascón
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Correspondence to José A. Gascón.

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Menikarachchi, L.C., Gascón, J.A. Optimization of cutting schemes for the evaluation of molecular electrostatic potentials in proteins via Moving-Domain QM/MM. J Mol Model 14, 1–9 (2008). https://doi.org/10.1007/s00894-008-0306-z

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  • DOI: https://doi.org/10.1007/s00894-008-0306-z

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