HERG CoMSiA model

Our studies also suggested that H-bond acceptors play an important role for compounds that bind the HERG channel (GRIND descriptors 13 and 34 in both the pharmacophoric models, as shown in Fig. 9.8). The statistical relevance of the MIFs generated by the hydrophobic probe confirmed the assumptions that were made in a previous CoMSiA model [17] regarding the presence of a hydrophobic feature. 

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

Pearlstein RA, Vaz Rl, Kang J, Chen X-L, Preobrazhenskaya M, Shchekotikhin AE et al. Characterisation of HERG Potassium channel inhibition using COMSiA 3D QSAR and homology modeling approaches. Bioorg Med Chem Lett 2003 13 1829-35. 

L. N., Miroshnikova, O.V., Hendrix, J., Rampe, D. Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches, Bioorg. Med. Chem. Lett. 2003, 13, 1829-1835. 

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