Yüksek Aslı, Yıkınç Batuhan, Nayır İrem, Alnıgeniş Defne, Fidan Vahap Gazi, Topuz Tayyip, Akten Ebru Demet
Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Kadir Has University, 34083 Fatih, Istanbul, Turkey.
Ph.D. Program of Computer Engineering, School of Graduate Studies, Kadir Has University, 34083 Fatih, Istanbul, Turkey.
J Chem Inf Model. 2025 Apr 14;65(7):3117-3126. doi: 10.1021/acs.jcim.4c01233. Epub 2025 Mar 27.
A total of 1311 homodimers were collected and analyzed in three different categories to highlight the impact of lipid environment and secondary structure type: 422 cytoplasmic α-helix, 411 cytoplasmic β-strand, and 478 membrane complexes. Structural features of the interface connecting two monomers were investigated and compared to those of the non-interface surface. Every residue on the surface of each monomer was explored based on four attributes: solvent-accessible surface area (SASA), protrusion index (C), surface planarity, and surface roughness. SASA and C distribution profiles clearly distinguished the interface from the surface in all categories, where the rim of the interface displayed higher SASA and C values than the rest of the surface. Surface residues in membrane complexes protruded less than cytoplasmic ones due to the hydrophobic environment, and consequently, the difference between surface and interface residues became less noticeable in that category. Cytoplasmic β-strand complexes displayed markedly lower SASA at the interface core than at the surface. The major distinction between the surface and interface was achieved through surface roughness, which displayed significantly higher values for the interface than the surface, especially in cytoplasmic complexes. Clearly, a surface which is relatively rugged favors the association of two monomers through multiple van der Waals interactions and hydrogen-bond formations. Another structural descriptor with strong distinguishing ability was surface planarity, which was higher at the interface than at the non-interface surface. Surface flatness would eventually facilitate the interconnectedness of an interface with a network of residue pairs bridging two complementary surfaces. Analysis of contact pairs revealed that hydrophobic pairs have the highest frequency of occurrence in the lipid environment of membrane complexes. However, despite the scarcity of polar residues at the interface, the likelihood of observing a contact between polar residues was markedly higher than that of hydrophobic ones.
共收集了1311个同型二聚体，并将其分为三类进行分析，以突出脂质环境和二级结构类型的影响：422个细胞质α螺旋、411个细胞质β链和478个膜复合物。研究了连接两个单体的界面的结构特征，并与非界面表面的结构特征进行了比较。基于四个属性对每个单体表面的每个残基进行了探索：溶剂可及表面积（SASA）、突出指数（C）、表面平面度和表面粗糙度。SASA和C分布曲线在所有类别中都能清楚地将界面与表面区分开来，其中界面边缘的SASA和C值高于表面的其他部分。由于疏水环境，膜复合物中的表面残基比细胞质中的残基突出程度小，因此，在该类别中，表面残基和界面残基之间的差异变得不那么明显。细胞质β链复合物在界面核心处的SASA明显低于表面处的SASA。表面和界面之间的主要区别是通过表面粗糙度实现的，界面的表面粗糙度值明显高于表面，尤其是在细胞质复合物中。显然，相对崎岖的表面有利于两个单体通过多个范德华相互作用和氢键形成而缔合。另一个具有强区分能力的结构描述符是表面平面度，界面处的表面平面度高于非界面表面。表面平整度最终将促进界面与连接两个互补表面的残基对网络的相互连接。接触对分析表明，疏水对在膜复合物的脂质环境中出现的频率最高。然而，尽管界面处极性残基稀少，但观察到极性残基之间接触的可能性明显高于疏水残基。
