Non-covalent interactions in biomolecules

In view of this and in line with the DFT-D approach described by Grimme [118], we have added an atom-atom pair-wise additive potential of the form C s/R6 to the usual semi-empirical energy [19-21] in order to account for dispersion effects [43], Thus the dispersion corrected semi-empirical energy ( Pm3-d) is now given by  

the summation is over all atom pairs, CV 7 is the dispersion coefficient for the pair of atoms i and j (calculated from the atomic CV, coefficients), s is a scaling factor which is chosen to be 1.4 in line with the value used for the BLYP functional [118], and Rij is the inter-atomic distance between atoms i and j. A damping function is used in order to avoid near singularities for small distances, given by  

The modification of the semi-empirical Hamiltonian thus required the development of a new set of parameters for use within the PM3 method. Rather than develop a new reference database we chose to use the high-level ab initio calculations recently reported by Hobza and co-workers [1]. These calculations have been collected together in a database which can be used to judge the accuracy of less rigorous, but 

We now compare the PM3-D method with previous uncorrected DFT calculations on the S22 complexes [130], For the dispersion-bonded complexes the errors in the interaction distances for the PBE, B3LYP and TPSS functionals are reported to be 0.63, 1.16 and 0.69 A which are reduced to 0.17, 0.00 and 0.02 A when appropriate dispersive corrections are included. We see in Table 5-9 that the PM3-D method is capable of predicting the structures of dispersion-bonded complexes with greater accuracy than some uncorrected DFT functionals and with an accuracy comparable to that for the dispersion corrected PBE functional [130], 

3 Calculated at the JSCH-2005 database geometries [1]. (In parenthesis) number of comparisons. b Mean signed error. c Mean deviation. d Mean unsigned error. e Root mean square error. 

Citrinin A turned out to be 0.6 kj/mol more stable than citrinin B. We discovered an unusual H - H interaction between the methyl group located at position 3 in Fig. 5 and one of the hydrogens attached to the ring. The corresponding bond critical point is marked in Fig. 6 as BCP . The two connected hydrogens (again marked) are 2.03 A apart. 

If H - H bonds widely occiu in biomolecules one may speculate what their full meaning is, in terms of the locahsation of molecular stabUity. Should the view of apolar side chains merely causing steric steering in protein folding be revised, and be replaced by one in which hydrocarbon fragments display as of yet unappreciated relationships of attraction QCT could also be instrumental in explaining frequently imexpected fragmentation patterns in peptide mass spectrometry. 

In the next section, I lodge a few remarks, perhaps of a rather philosophical nature, that may help in outUning new (computational) experiments to solve the problem of bonding. Let me apologise beforehand for the utterly raw and untested nature of these ideas. 

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