Optimization of cutting schemes for the evaluation of molecular electrostatic potentials in proteins via Moving-Domain QM/MM |
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Authors: | Lochana C Menikarachchi José A Gascón |
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Institution: | (1) Department of Chemistry, University of Connecticut, 55 North Eagleville Rd, Unit 3060, Storrs, CT 06269, USA |
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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 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.
Figure Schematic representation of the Moving Domain QM/MM method |
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Keywords: | Molecular electrostatic potential Moving-Domain QM/MM Polarization |
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