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J Biomol Struct Dyn. 2016;34(3):540-59. doi: 10.1080/07391102.2015.1044474. Epub 2015 May 21.

The effect of various atomic partial charge schemes to elucidate consensus activity-correlating molecular regions: a test case of diverse QSAR models.

Author information

1
a Department of Bioinformatics , Applied Botany Centre (ABC), University School of Sciences, Gujarat University , Ahmedabad 380 009 , India.
2
b School of Chemical Sciences, Central University of Gujarat , Sector-30, Gandhinagar 382030 , India.

Abstract

The estimation of atomic partial charges of the small molecules to calculate molecular interaction fields (MIFs) is an important process in field-based quantitative structure-activity relationship (QSAR). Several studies showed the influence of partial charge schemes that drastically affects the prediction accuracy of the QSAR model and focused on the selection of appropriate charge models that provide highest cross-validated correlation coefficient ([Formula: see text] or q(2)) to explain the variation in chemical structures against biological endpoints. This study shift this focus in a direction to understand the molecular regions deemed to explain SAR in various charge models and recognize a consensus picture of activity-correlating molecular regions. We selected eleven diverse dataset and developed MIF-based QSAR models using various charge schemes including Gasteiger-Marsili, Del Re, Merck Molecular Force Field, Hückel, Gasteiger-Hückel, and Pullman. The generalized resultant QSAR models were then compared with Open3DQSAR model to interpret the MIF descriptors decisively. We suggest the regions of activity contribution or optimization can be effectively determined by studying various charge-based models to understand SAR precisely.

KEYWORDS:

COX-2 inhibitors; atomic partial charge schemes; consensus descriptors; field-based QSAR; molecular interaction fields

PMID:
25997097
DOI:
10.1080/07391102.2015.1044474
[Indexed for MEDLINE]

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