Sierra María Belén, Accordino Sebastián R, Rodriguez-Fris J Ariel, Morini Marcela A, Appignanesi Gustavo A, Fernández Stigliano Ariel
Sección Fisicoquímica, INQUISUR-UNS-CONICET-Departamento de Química, Universidad Nacional del Sur, Avda. Alem 1253, 8000, Bahía Blanca, Argentina.
Eur Phys J E Soft Matter. 2013 Jun;36(6):62. doi: 10.1140/epje/i2013-13062-7. Epub 2013 Jun 25.
Ligands must displace water molecules from their corresponding protein surface binding site during association. Thus, protein binding sites are expected to be surrounded by non-tightly-bound, easily removable water molecules. In turn, the existence of packing defects at protein binding sites has been also established. At such structural motifs, named dehydrons, the protein backbone is exposed to the solvent since the intramolecular interactions are incompletely wrapped by non-polar groups. Hence, dehydrons are sticky since they depend on additional intermolecular wrapping in order to properly protect the structure from water attack. Thus, a picture of protein binding is emerging wherein binding sites should be both dehydrons rich and surrounded by easily removable water. In this work we shall indeed confirm such a link between structure and dynamics by showing the existence of a firm correlation between the degree of underwrapping of the protein chain and the mobility of the corresponding hydration water molecules. In other words, we shall show that protein packing defects promote their local dehydration, thus producing a region of "hot" interfacial water which might be easily removed by a ligand upon association.
配体在结合过程中必须从相应蛋白质表面结合位点取代水分子。因此，预计蛋白质结合位点周围会存在非紧密结合、易于去除的水分子。反过来，蛋白质结合位点处堆积缺陷的存在也已得到证实。在这种被称为脱水子的结构基序中，由于分子内相互作用未被非极性基团完全包裹，蛋白质主链暴露于溶剂中。因此，脱水子具有粘性，因为它们需要额外的分子间包裹来适当保护结构免受水的攻击。因此，一幅蛋白质结合的图景正在浮现，其中结合位点应该既富含脱水子又被易于去除的水所包围。在这项工作中，我们确实将通过展示蛋白质链未包裹程度与相应水化水分子流动性之间存在紧密相关性来证实结构与动力学之间的这种联系。换句话说，我们将表明蛋白质堆积缺陷会促进其局部脱水，从而产生一个“热”界面水区域，配体在结合时可能很容易将其去除。
