Shin Woong-Hee, Kumazawa Keiko, Imai Kenichiro, Hirokawa Takatsugu, Kihara Daisuke
Department of Chemistry Education, Sunchon National University, Suncheon, South Korea.
Department of Advanced Components and Materials Engineering, Sunchon National University, Suncheon, South Korea.
Front Mol Biosci. 2023 Feb 6;10:1110567. doi: 10.3389/fmolb.2023.1110567. eCollection 2023.
Driving mechanisms of many biological functions in a cell include physical interactions of proteins. As protein-protein interactions (PPIs) are also important in disease development, protein-protein interactions are highlighted in the pharmaceutical industry as possible therapeutic targets in recent years. To understand the variety of protein-protein interactions in a proteome, it is essential to establish a method that can identify similarity and dissimilarity between protein-protein interactions for inferring the binding of similar molecules, including drugs and other proteins. In this study, we developed a novel method, protein-protein interaction-Surfer, which compares and quantifies similarity of local surface regions of protein-protein interactions. protein-protein interaction-Surfer represents a protein-protein interaction surface with overlapping surface patches, each of which is described with a three-dimensional Zernike descriptor (3DZD), a compact mathematical representation of 3D function. 3DZD captures both the 3D shape and physicochemical properties of the protein surface. The performance of protein-protein interaction-Surfer was benchmarked on datasets of protein-protein interactions, where we were able to show that protein-protein interaction-Surfer finds similar potential drug binding regions that do not share sequence and structure similarity. protein-protein interaction-Surfer is available at https://kiharalab.org/ppi-surfer.
细胞中许多生物学功能的驱动机制包括蛋白质的物理相互作用。由于蛋白质-蛋白质相互作用（PPI）在疾病发展中也很重要，近年来，蛋白质-蛋白质相互作用在制药行业中作为可能的治疗靶点而备受关注。为了理解蛋白质组中各种蛋白质-蛋白质相互作用，建立一种能够识别蛋白质-蛋白质相互作用之间的相似性和差异性以推断包括药物和其他蛋白质在内的相似分子结合情况的方法至关重要。在本研究中，我们开发了一种新方法——蛋白质-蛋白质相互作用搜索器（protein-protein interaction-Surfer），该方法可比较和量化蛋白质-蛋白质相互作用局部表面区域的相似性。蛋白质-蛋白质相互作用搜索器用重叠的表面斑块来表示蛋白质-蛋白质相互作用表面，每个斑块都用三维泽尼克描述符（3DZD）进行描述，3DZD是一种三维函数的紧凑数学表示形式。3DZD既能捕捉蛋白质表面的三维形状，又能捕捉其物理化学性质。蛋白质-蛋白质相互作用搜索器的性能在蛋白质-蛋白质相互作用数据集上进行了基准测试，我们能够证明蛋白质-蛋白质相互作用搜索器能找到不具有序列和结构相似性的相似潜在药物结合区域。蛋白质-蛋白质相互作用搜索器可在https://kiharalab.org/ppi-surfer获取。
