Quantum refinement

Nilsson K et al (2004) The protonation status of compound II in myoglobin, studied by a combination of experimental data and quantum chemical calculations quantum refinement. Biophys J 87(5) 3437-3447... 

Nilsson K, Ryde U (2004) Protonation status of metal-bound ligands can be determined by quantum refinement. J Inorg Biochem 98(9) 1539—1546... 

First Steps Towards Quantum Refinement of Protein X-Ray Structures... 

Lysozyme crystallizes in different polymorphic space groups depending on the crystallization conditions [42]. Very recently, Falklof et al. [43] carried out an analysis of triclinic hen egg-white lysozyme (HEWL) published by Wang et al. [42] (structure 2VB1 in the PDB). Their analysis serves as starting point for our quantum refinement approach. 

Nilsson K, Lecerof D, Sigfridsson E, Ryde U (2003) An automatic method to generate force-field parameters for hetero-compounds. Acta CrystaUogr, D-Biol CrystaUogr 59 274—289 Nilsson K, Ryde U (2004) Protonation status of metal-bound hgands can be determined by quantum refinement. J Inorg Biochem 98 1539-1546... 

Ryde U, Nilsson K (2003) Quantum refinement—a combination of quantum chemistry and protein crystallography. J Mol Struct, Theochem 632 259-275... 

Hsiao YW, Sanchez-Garcia E, Doerr M, Thiel W (2010) Quantum refinement of protein structures implementation and application to the red fluorescent protein DsRed.Ml. J Phys ChemB 114 15413-15423... 

In a similar fashion, Catana and Stouten [143] developed multiple functions based on QXP protein-ligand interaction terms [112]. The concept was also applied for improving a force field-based scoring function for CDK-2 using short MD simulations based on quantum-refined force fields [144]. Here, the statistical analysis of... 

New scoring functions for virtual screening from moleculat dynamics simulations with a Quantum-Refined Force-Field (QRFF-MD). Application to cyclin-dependent kinase 2. Journal of Chemical Information and Modeling, 46, 254-263. 

An example is the quantum-refined crystal structure of cytochrome C 553 from Bacillus pastcurii. X-ray diffraction data has been obtained at two different resolutions (1.7 A and 0.97 A). Based on the low-resolution data, a quantum refinement procedure as described above was used. As can be seen from Table 7.1, the quantum-mechanically refined low resolution data reads a quality which almost match the quality of the high-resolution data. 

The m-vacuum D FT structural data are also shown in Table 7.1, and these are almost identical to the high-resolution structure. Therefore, the assumption is made that the geometry of the metal sites in proteins is almost identical to the structure in vacuo [288]. This may often - but not always - be the case. Also, it must be borne in mind that the quantum refinement itself is limited by the quality of the QM method used. It is... 

Table 7.1 Fe-ligand distances at low (1.7 A) resolution, high (0.97 A) resolution, quantum refined from the low-resolution data and calculated via DFT (BP86/6-31C ) in vacuo. Data taken from Ref [288].

L. Goerigk, O. Falklof, C.A. CoUyer, J.R. Reimers, First steps towards quantum refinement of protein X-ray structures, in J. Zeng, R.-Q. Zhang, H.R. Treudein (Eds.), Springer, Netherlands, 2012, pp. 87-121. 

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