Fragment-based modelling approach

Plate 16 A summary of the fragment-based modelling approach. 

A potent inhibitor of the serine/threonine Jun N-terminal Kinase 3 (JNK3) was identified after using a fragment-based NMR approach. A follow-up study with competition-binding methods and molecular docking based on the crystal structure of JNK3 proposed potential binding models. These models were used in turn to synthesize a set of several thousand optimized compounds... 

A skewed Gaussian-type distribution function can depict the yield distributions. The resulting model reproduces published pilot-plant and commercial data on vacuum gas oil hydrocracking.This has led to the development of a hydrocracking process model." Selective cracking in FCC has also been addressed.Browarzik and Kehlen used a fragmentation-based model for n-alkane hydrocracking. Similar approaches have been used for polymer reaction systems." " ... 

The integral spray-process modelling will take account of three sub-processes, that is liquid sheet fragmentation, droplet spray, and particle formation. In the CFD-based modelling approach, the liquid fragmentation will be modelled based on a modified volume of fluid (VOF) approach, while the droplet spray and particle... 

Moriaud F, Doppelt-Azeroual O, Martin L et al (2009) Computational fragment-based approach at PDB scale by protein local similarity. J Chem Inf Model 49 280-294... 

Richards, N., Williams, P. B., and Tute, M. (1991) Empirical methods for computing molecular partition coefficients. I. Upon the need to model the specific hydration of polar groups in fragment based approaches. Int. J. Quant. Chem. 18, 299-316. 

Durrant JD, Friedman AJ, McCammon JA (2011) CrystalDock a novel approach to fragment-based drug design. J Chem Inf Model 51 2573-2580. doi 10.1021/ci200357y... 

M.S. Gordon, M.A. Freitag, P. Bandyopadhyay, J.H. Jensen, V. Kairys, W.J. Stevens, The effective fragment potential method A QM-based MM approach to modeling environmental effects in chemistry, J. Phys. Chem. A105 (2001) 293. 

We performed a combined 2D and 3D analysis of chemical and biological space to identify ion channel privileged chemotypes. The 2D approach was based on a collection of biologically active compounds and consisted mainly of similarity and substructure searching and of analysis of common frameworks and fragments. Our 3D approach relied on multiple ion channel pharmacophores and homology models, which were used for virtual screening. 

---