====== Manganese(II) - ED[PY2]WaWa ======
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In Pyruvate Kinase manganese(II) mediates the allosteric communication between the phosphoenolpyruvate and fructose-1,6-bisphosphate.
Crystal structures suggest that manganese(II) bonds to aspartate, glutamate and the oxygen from a carbonyl and carboxylate groups from a pyruvate ligand.
A water molecule is referred as participating in the octahedral coordination of manganese(II).
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| **COORDINATION SPHERE** ||
| {{ :mm:parameters:manganese:non-parameterized_edpy2ww_.png?120 |}} | \\ **Oxidation State:** Mn(II) \\ **Spin Multiplicity:** 6 |
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===== Structure chosen to parameterize =====
| **TEST PROTEIN** ||
| //Protein// | Pyruvate Kinase |
| //PDB Code// | 2G50 |
| //Crystallographic Resolution// | 1.65 Å |
| //Organism// | Oryctolagus cuniculus |
| [[http://pubs.acs.org/doi/abs/10.1021/bi0524262 | [Williams, 2006]]] ||
===== Parameters Determined =====
==== Atom Types ====
| **ATOM TYPE** | **NEW ATOM TYPE** | **MASS** | **STRUCTURE** |
| MN | M1 | 54.938 | {{ :mm:parameters:manganese:parameterized_edpy2ww_.png?120 |}} |
| OD2 | D1 | 15.9994 | ::: |
| OE1 | E1 | 15.9994 | ::: |
| OW | W1 | 15.9994 | ::: |
| OW | W2 | 15.9994 | ::: |
| HW | HM | 1.00794 | ::: |
==== Bond Parameters ====
| **BOND** | **Kl** / **kcal mol-1 Å-2** | **l / Å** | **REFERENCE** |
| M1-D1 | 71.90 | 2.0926 | [[#references | [Neves, 2013]]] |
| M1-E1 | 68.77 | 2.1399 | ::: |
| M1-R1 | 55.39 | 2.1382 | ::: |
| M1-R2 | 16.78 | 2.4332 | ::: |
| M1-W1 | 24.75 | 2.3873 | ::: |
| M1-W2 | 50.08 | 2.2004 | ::: |
| D1-C | 656.0 | 1.25 |
| E1-C | 656.0 | 1.25 |
| W1-HM | 553.0 | 0.9572 |
| W2-HM | 553.0 | 0.9572 |
| c-R2 | 648.0 | 1.214 |
| c-R1 | 648.0 | 1.214 |
==== Angle Parameters ====
| **ANGLE** | **Kθ** / **kcal mol-1 rad-2** | **θ / deg** | **REFERENCE** |
| D1-M1-E1 | 38.27 | 96.6209 | [[#references | [Neves, 2013]]] |
| D1-M1-R1 | 23.41 | 104.8054 | ::: |
| D1-M1-R2 | 12.445 | 169.3708 | ::: |
| D1-M1-W1 | 69.3 | 72.8299 | ::: |
| D1-M1-W2 | 26.19 | 103.5245 | ::: |
| E1-M1-R1 | 29.696 | 97.7449 | ::: |
| E1-M1-R2 | 13.94 | 93.9317 | ::: |
| E1-M1-W1 | 25.05 | 168.0717 | ::: |
| E1-M1-W2 | 52.2 | 89.0644 | ::: |
| R1-M1-R2 | 128.3 | 80.3387 | ::: |
| R1-M1-W1 | 20.47 | 80.0896 | ::: |
| R1-M1-W2 | 18.05 | 149.8517 | ::: |
| R2-M1-W1 | 13.736 | 96.5418 | ::: |
| R2-M1-W2 | 27.09 | 77.9339 | ::: |
| W1-M1-W2 | 15.008 | 98.6963 | ::: |
| M1-D1-C | 14.829 | 125.0463 | ::: |
| M1-E1-C | 42.056 | 122.8295 | ::: |
| M1-R1-c | 47.47 | 122.0775 | ::: |
| M1-R2-c | 57.66 | 110.2798 | ::: |
| M1-W1-HM | 12.10 | 86.3993 | ::: |
| M1-W2-HM | 28.96 | 88.1336 | ::: |
| HM-W1-HM | 100.0 | 104.52 |
| HM-W2-HM | 100.0 | 104.52 |
| HM-W3-HM | 100.0 | 104.52 |
| D1-C-CT | 70.0 | 117.0 |
| D1-C-O2 | 80.0 | 126.0 |
| E1-C-CT | 70.0 | 117.0 |
| E1-C-O2 | 80.0 | 126.0 |
| c3-c-R2 | 68.0 | 123.11 |
| R1-c-c | 66.8 | 122.34 |
| o-c-R1 | 79.1 | 127.33 |
| c-c-R2 | 66.8 | 122.34 |
==== Van der Waals Parameters ====
| **ATOM TYPE** | **Ri / Å** | **εi / kcal mol-1** | **REFERENCE** |
| M1 | 1.4544 | 0.03 | [[http://pubs.acs.org/doi/abs/10.1021/jp054177x | [Babu, 2006]]] |
| D1 | 1.6612 | 0.21 |
| E1 | 1.6612 | 0.21 |
| R1 | 1.6612 | 0.2100 |
| R2 | 1.6612 | 0.2100 |
| W1 | 1.7683 | 0.152 |
| W2 | 1.7683 | 0.152 |
| HM | 0.6000 | 0.0157 | [[http://pubs.acs.org/doi/abs/10.1021/ja00124a002 | [Cornell, 1995]]] |
===== Validation of Parameters from MD Simulations =====
==== Bond Parameters ====
| **BOND** | **l0 crystal** | **l0 opt** | **‹l›MD ± σ(l)** | **‹l›MD ± 2σ(l)** |
| M1-D1 | 1.97 | 2.09 | 2.16 ± 0.06 | [2.095; 2.225] |
| M1-E1 | 1.96 | 2.14 | 2.22 ± 0.06 | [2.153; 2.281] |
| M1-R1 | 1.98 | 2.14 | 2.13 ± 0.07 | [2.059; 2.192] |
| M1-R2 | 1.95 | 2.43 | 2.4 ± 0.1 | [2.276; 2.473] |
| M1-W1 | 2.29 | 2.39 | 2.4 ± 0.1 | [2.289; 2.537] |
| M1-W2 | 2.26 | 2.20 | 2.18 ± 0.08 | [2.100; 2.258] |
==== Angle Parameters ====
| **ANGLE** | **θ0 crystal** | **θ0 QM** | **‹θ›MD ± σ(θ)** | **‹θ›MD ± 2σ(θ)** |
| D1-M1-E1 | 97.0 | 96.6 | 99 ± 5 | [89.0; 108.1] |
| D1-M1-R1 | 90.8 | 104.8 | 103 ± 5 | [93.1; 112.4] |
| D1-M1-R2 | 153.6 | 169.4 | 170 ± 5 | [159.4; 180.1] |
| D1-M1-W1 | 78.1 | 72.8 | 75 ± 4 | [67.8; 82.2] |
| D1-M1-W2 | 113.2 | 103.5 | 110 ± 5 | [99.5; 120.6] |
| E1-M1-R1 | 91.7 | 97.7 | 101 ± 5 | [91.1; 110.3] |
| E1-M1-R2 | 105.0 | 93.9 | 75 ± 5 | [64.3; 86.1] |
| E1-M1-W1 | 163.9 | 168.1 | 168 ± 4 | [159.5; 176.5] |
| E1-M1-W2 | 84.8 | 89.1 | 80 ± 4 | [71.4; 87.7] |
| R1-M1-R2 | 74.4 | 80.3 | 75 ± 2 | [70.9; 79.1] |
| R1-M1-W1 | 103.6 | 80.1 | 79 ± 7 | [63.7; 93.7] |
| R1-M1-W2 | 156.0 | 149.9 | 146 ± 5 | [136.7; 155.4] |
| R2-M1-W1 | 84.2 | 96.5 | 111 ± 7 | [97.0; 124.2] |
| R2-M1-W2 | 83.5 | 77.9 | 73 ± 5 | [63.3; 82.5] |
| W1-M1-W2 | 83.1 | 98.7 | 105 ± 10 | [85.6; 123.9] |
===== Downloads =====
| //Parameter File// | {{:mm:parameters:manganese:ed_py2_ww-frcmod.zip| .frcmod}} |
| //Coordination Sphere Charges// | {{:mm:parameters:manganese:ed[py2]ww_mn-ii.zip| .off}} |
| //Pyruvate Kinase’s PDB File (2G50.pdb)\\ LEAPRC file// | {{:mm:parameters:manganese:pyruvate_kinase.zip| .pdb, leaprc}} |
===== References =====
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Neves, R.P.P.; Sousa, S.F.; Fernandes, P.A.; Ramos, M.J.. [[http://pubs.acs.org/doi/abs/10.1021/ct400055v | Parameters for Molecular Dynamics Simulations of Manganese-Containing Metalloproteins]] . //J. Chem. Theory Comput.//, **2013**, 9 (6), 2718–2732
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