title: Optimization of cutting schemes for the evaluation of molecular electrostatic potentials in proteins via Moving-Domain QM/MM.
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.
authors.affiliation: Department of Chemistry, University of Connecticut, 55 North Eagleville Rd, Unit 3060, Storrs, CT 06269, USA.
authors.forename: Lochana C
authors.initials: LC
authors.lastname: Menikarachchi
authors.forename: José A
authors.initials: JA
authors.lastname: Gascón
mesh_terms: D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000737:chemistry; D003198:Computer Simulation; D006096:Gramicidin / Q000737:chemistry; D008956:Models, Chemical; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D011506:Proteins; D006096:Gramicidin