Taxol computational studies

Computational studies have been of paramount importance in order to integrate the results of the experimental studies indicated above with the electron crystallographic data known. According to Snyder and co-workers, a satisfactory and experimentally verifiable model of the tubulin-binding site and of the conformation of paclitaxel has been obtained by computational methods on the first electron crystallographic model. In this context, a new paclitaxel conformer, T-Taxol (Fig. 10c), was proposed [59, 81, 82],... 

Another conformation different from T-taxol was proposed based on molecular dynamics simulations and computational docking restrained by the two REDOR distances [85], The main difference between this conformer (named REDOR-taxol or PTX-NY) and T-taxol is the conformation of the C13 side chain, that places the 2 -OH in a different orientation. However, subsequent studies demonstrated that PTX-NY is not consistent with the EC density [86, 87],... 

Recently, we proposed a new bioactive conformation of paclitaxel, RKDOR-Taxol [50], based on (i) the 19F-13C distances obtained by the REDOR experiment [49], (ii) the photoaffinity labeling of microtubules [51], (iii) the crystal structure (PDB code 1TUB) of the Zn2+-stabilized aP-tubulin dimer model determined by cryo-electron microscopy (cryo-EM) [52], and (iv) molecular modeling (Monte Carlo Macromodel) [50], In this computational biology analysis, we first docked a paclitaxel-photoaffinity label molecule to the position identified by our photoaffinity labeling study and then optimized the... 

Braga, S.F. and Galvao, D.S. (2003) A structure-activity study of taxol, taxotere, and derivatives using the electronic indices methodology (EIM). /. Chem. Inf. Comput. Sci., 43, 699—706. 

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