Haddad Yazan, Adam Vojtěch, Heger Zbyněk
Department of Chemistry and Biochemistry, Mendel University in BrnoBrno, Czechia.
Central European Institute of Technology, Brno University of TechnologyBrno, Czechia.
Front Mol Neurosci. 2017 May 3;10:130. doi: 10.3389/fnmol.2017.00130. eCollection 2017.
Some therapeutic side-effects result from simultaneous activation of homolog receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC) play a major role in the development and biology of neurons through neurotrophin signaling. The wide range of cross-interactions between Trk receptors and neurotrophins vary in selectivity, affinity and function. In this study, we discuss new perspectives to the manipulation of side-effects via a better understanding of the cross-interactions at the molecular level, derived by computational methods. Available crystal structures of Trk receptors and neurotrophins are a valuable resource for exploitation via molecular mechanics (MM) and dynamics (MD). The study of the energetics and dynamics of neurotrophins or neurotrophic peptides interacting with Trk receptors will provide insight to structural regions that may be candidates for drug targeting and signaling pathway selection.
一些治疗副作用是由同一配体同时激活同源受体引起的。原肌球蛋白受体激酶（TrkA、TrkB和TrkC）通过神经营养因子信号传导在神经元的发育和生物学过程中发挥主要作用。Trk受体与神经营养因子之间广泛的交叉相互作用在选择性、亲和力和功能方面存在差异。在本研究中，我们通过计算方法对分子水平上的交叉相互作用有了更好的理解，从而探讨了控制副作用的新观点。Trk受体和神经营养因子的现有晶体结构是通过分子力学（MM）和动力学（MD）进行开发的宝贵资源。对与Trk受体相互作用的神经营养因子或神经营养肽的能量学和动力学研究将为可能成为药物靶点和信号通路选择候选的结构区域提供见解。
