Walker Alice R, Bonomi Robin, Popov Vadim, Gelovani Juri G, Andrés Cisneros G
Department of Chemistry, Wayne State University, Detroit, MI 48202, United States.
Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, United States.
J Mol Graph Model. 2017 Jan;71:211-217. doi: 10.1016/j.jmgm.2016.10.018. Epub 2016 Nov 25.
Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity.
半乳糖凝集素-3（Gal-3）是一种碳水化合物结合蛋白，在包括胰腺癌在内的多种癌症中过表达，这使其成为成像和治疗药物设计的良好靶点。已使用分子动力学（MD）和自由能方法研究了专门用于氟正电子发射断层扫描（PET）的配体库，以确定各种潜在配体的相对结合能。我们的结果表明，对于这类配体，传统对接方法在辅以分子动力学和自由能方法时可以给出良好的结果。少数测试化合物的可用实验结合亲和力与计算出的能量非常吻合，并为设计具有更高亲和力的Gal-3配体提供了合理的方法。
