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Application of a simple quantum chemical approach to ligand fragment scoring for Trypanosoma brucei pteridine reductase 1 inhibition.

Abstract：

:There is a need for improved and generally applicable scoring functions for fragment-based approaches to ligand design. Here, we evaluate the performance of a computationally efficient model for inhibitory activity estimation, which is composed only of multipole electrostatic energy and dispersion energy terms that approximate long-range ab initio quantum mechanical interaction energies. We find that computed energies correlate well with inhibitory activity for a compound series with varying substituents targeting two subpockets of the binding site of Trypanosoma brucei pteridine reductase 1. For one subpocket, we find that the model is more predictive for inhibitory activity than the ab initio interaction energy calculated at the MP2 level. Furthermore, the model is found to outperform a commonly used empirical scoring method. Finally, we show that the results for the two subpockets can be combined, which suggests that this simple nonempirical scoring function could be applied in fragment-based drug design.

journal_name

J Comput Aided Mol Des

journal_title

Journal of computer-aided molecular design

authors

Jedwabny W,Panecka-Hofman J,Dyguda-Kazimierowicz E,Wade RC,Sokalski WA

doi

10.1007/s10822-017-0035-4

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

715-728

issue

8

eissn

0920-654X

issn

1573-4951

pii

10.1007/s10822-017-0035-4

journal_volume

31

pub_type

杂志文章

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