Using Surface Scans for the Evaluation of Halogen Bonds toward the Side Chains of Aspartate, Asparagine, Glutamate, and Glutamine
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- 作者：Markus O. Zimmermann ; Andreas Lange ; Stefan Zahn ; Thomas E. Exner ; Frank M. Boeckler
- 刊名：Journal of Chemical Information and Modeling
- 出版年：2016
- 出版时间：July 25, 2016
- 年：2016
- 卷：56
- 期：7
- 页码：1373-1383
- 全文大小：664K
- 年卷期：0
- ISSN：1549-960X
文摘
Using halogen-specific Connolly type molecular surfaces, we herein invented a new type of surface-based interaction analysis employed for the study of halogen bonding toward model systems of biologically relevant carboxylates (ASP/GLU) and carboxamides (ASN/GLN). Database mining and statistical assessment of the PDB revealed that such interactions are widely underrepresented at the moment. We observed important distance-dependent adaptions of the binding modes of halobenzenes from a preferential oxygen-directed to a bifurcated interaction geometry of the carboxylate. In addition, halogen···π contacts perpendicular to the nitrogen atom of the carboxamide become increasingly important for the lighter halogens. Our analysis on a MP2/TZVPP level of theory is backed by CCSD(T)/CBS reference calculations. To put the vast interaction energies into perspective, we also performed COSMO-RS calculations of the solvation free energy. Facilitating the visualization of our results mapped onto any binding site of choice, we aim to inspire more design studies showcasing these underrepresented interactions.