====== Zinc (II) - HDC ======
The metal center of Farnesyltransferase in the resting state is hereby presented, in which the Zinc atom is bonded to 1 histidine, 1 cysteine and to 1 aspartate (bidentate). Validation for the binary complex is additionally provided.
| **Coordination Sphere** | **Oxidation state:** Zn(II) \\ **Spin multiplicity:** 1 |
| {{ :mm:parameters:zinc:set1.png?120 |}} | JMOL |
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===== Structure chosen to parameterize =====
| **TEST PROTEIN** ||
| //Protein// | Farnesyltransferase |
| //PDB Code// | 1FT1 |
| //Crystallographic Resolution// | 2.25 Å |
| //Organism// | //Rattus norvegicus// |
| [[http://www.ncbi.nlm.nih.gov/pubmed/9065406 | [Park, 1997]]] ||
===== Parameters Determined =====
==== Atom Types ====
| **ATOM TYPE** | **NEW ATOM TYPE** | **MASS** | **STRUCTURE** |
| ZN | ZF | 65.409 | {{ :mm:parameters:zinc:set1_molecule.png?120 |}} |
| NE2 | NF | 14.0067 | ::: |
| OD2 | OF | 15.9994 | ::: |
| OD1 | OG | 15.9994 | ::: |
| SG | SF | 32.065 | ::: |
==== Bond Parameters ====
| **BOND** | **Kl** / **kcal mol-1 Å-2** | **l / Å** | **REFERENCE** |
| ZF-NF | 88.3 | 2.043 | [[#references | [Sousa, 2007]]] |
| ZF-OF | 62.3 | 2.094 | ::: |
| ZF-OG | 43.8 | 2.159 | ::: |
| ZF-SF | 115.8 | 2.258 | ::: |
| C-OF | 656.0 | 1.308 | ::: |
| C-OG | 656.0 | 1.306 | ::: |
| CT-SF | 227.0 | 1.903 | ::: |
| NF-CR | 477.0 | 1.338 | ::: |
| NF-CV | 427.0 | 1.401 | ::: |
==== Angles Parameters ====
| **ANGLE** | **Kθ** / **kcal mol-1 rad-2** | **θ / deg** | **REFERENCE** |
| OF-ZF-OG | 318.9 | 63.5 | [[#references | [Sousa, 2007]]] |
| OF-ZF-NF | 16.7 | 107.3 | ::: |
| OF-ZF-SF | 16.5 | 126.6 | ::: |
| OG-ZF-NF | 19.4 | 97.0 | ::: |
| OG-ZF-SF | 15.4 | 136.9 | ::: |
| NF-ZF-SF | 16.2 | 114.5 | ::: |
| C-OF-ZF | 10.0 | 90.8 | ::: |
| C-OG-ZF | 10.0 | 88.0 | ::: |
| CT-SF-ZF | 18.9 | 101.7 | ::: |
| CV-NF-ZF | 20.0 | 127.9 | ::: |
| CR-NF-ZF | 20.0 | 124.8 | ::: |
| OF-C-OG | 80.0 | 117.8 | ::: |
| CT-C-OF | 70.0 | 120.8 | ::: |
| CT-C-OG | 70.0 | 121.5 | ::: |
| NF-CV-H4 | 35.0 | 125.2 | ::: |
| H5-CR-NF | 35.0 | 121.0 | ::: |
| CR-NF-CV | 70.0 | 107.3 | ::: |
| NA-CR-NF | 70.0 | 109.5 | ::: |
| CC-CV-NF | 70.0 | 109.5 | ::: |
| CR-NF-CV | 70.0 | 107.3 | ::: |
| NA-CR-NF | 70.0 | 109.5 | ::: |
| CC-CV-NF | 70.0 | 109.5 | ::: |
| CT-CM-CT | 70.0 | 113.8 | ::: |
| CM-CM-CM | 70.0 | 122.8 | ::: |
| H1-CT-SF | 50.0 | 109.5 | |
| CT-CT-SF | 50.0 | 114.7 | ::: |
==== Van der Waals Parameters ====
| **ATOM TYPE** | **Ri / Å** | **εi / kcal mol-1** | **REFERENCE** |
| ZF | 1.7000 | 0.0125 | [[http://www.ncbi.nlm.nih.gov/pubmed/7716168 | [Ryde, 1995]]] |
| OF | 1.6612 | 0.2100 | |
| OG | 1.6612 | 0.2100 | ::: |
| SF | 2.0000 | 0.2500 | ::: |
| NF | 1.8240 | 0.1700 | ::: |
===== Validation of Parameters from MD Simulations =====
==== Bond Parameters ====
| **BOND** | **l0 crystal** | **‹l›MD ± σ(l) (Resting State)** | **‹l›MD ± σ(l) (Binary Complex)** |
| ZF-OF | 2.00 | 2.06 ± 0.06 | 2.09 ± 0.06 |
| ZF-OG | 2.56 | 2.15 ± 0.07 | 2.13 ± 0.07 |
| ZF-SF | 2.22 | 2.23 ± 0.05 | 2.24 ± 0.05 |
| ZF-NF | 2.48 | 2.02 ± 0.06 | 2.03 ± 0.06 |
==== Angle Parameters ====
| **ANGLE** | **θ0 crystal** | **‹θ›MD ± σ(θ) (Resting State)** | **‹θ›MD ± σ(θ) (Binary Complex)** |
| NF-ZF-SF | 118 | 119 ± 5 | 114 ± 6 |
| OF-ZF-NF | 120 | 101 ± 6 | 102 ± 7 |
| OF-ZF-OG | 56 | 64 ± 1 | 63 ± 1 |
| OF-ZF-SF | 104 | 124 ± 6 | 124 ± 6 |
| OG-ZF-NF | 90 | 81 ± 4 | 80 ± 5 |
| SF-ZF-OG | 80 | 84 ± 6 | 83 ± 6 |
===== Downloads =====
| //Parameter File// | {{:mm:parameters:zinc:hdc_zn-II.frcmod.zip| .frcmod}} |
| //Coordination Sphere Charges// | {{:mm:parameters:zinc:lib_files_1.zip| .lib}} |
| //LEAPRC file// | {{:mm:parameters:zinc:leaprc.zip| leaprc}} |
===== References =====
Sousa, S.F.; Fernandes, P.A.; Ramos, M.J.. [[http://link.springer.com/article/10.1007%2Fs00214-006-0170-9 | Effective tailor-made force field parameterization of the several Zn coordination environments in the puzzling FTase enzyme: opening the door to the full understanding of its elusive catalytic mechanism]] . //Theoretical Chemistry Accounts//, **2007**, 117, 171-181