Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093, Warsaw, Poland.
Eur Biophys J. 2023 Oct;52(6-7):559-568. doi: 10.1007/s00249-023-01653-0. Epub 2023 May 12.
In the vast majority of biologically relevant cases of receptor-ligand complex formation, the binding site of the receptor is a small part of its surface, and moreover, formation of a biologically active complex often requires a specific orientation of the ligand relative to the binding site. Before the formation of the initial form of the complex, only long-range, electrostatic and hydrodynamic interactions can act between the ligand approaching the binding site and the receptor. In this context, the question arises whether as a result of these interactions, there is a pre-orientation of the ligand towards the binding site, which to some extent would accelerate the formation of the complex. The role of electrostatic interactions in the orientation of the ligand relative to the binding site of the receptor is well documented. The analogous role of hydrodynamic interactions, although assessed as very significant by Brune and Kim (PNAS 91, 2930-2934, (1994)), is still debatable. In this article, I present the current state of knowledge on this subject and consider the possibilities of demonstrating the orienting effect of hydrodynamic interactions in the processes of receptor-ligand association, in an experimental way supported by computer simulations.
在绝大多数与生物学相关的受体-配体复合物形成的情况下,受体的结合位点只是其表面的一小部分,而且,形成具有生物活性的复合物通常需要配体相对于结合位点的特定取向。在复合物初始形式形成之前,只有配体接近结合位点和受体之间的长程、静电和流体动力相互作用才能起作用。在这种情况下,就会产生一个问题,即这些相互作用是否会导致配体预先朝向结合位点定向,从而在一定程度上加速复合物的形成。静电相互作用在配体相对于受体结合位点的定向中的作用已得到充分证明。虽然 Brune 和 Kim(PNAS 91,2930-2934,(1994))评估了流体动力相互作用的类似作用,但它仍然存在争议。本文介绍了这一主题的最新知识,并考虑了通过计算机模拟实验支持的方法来证明流体动力相互作用在受体-配体结合过程中的定向作用的可能性。