Liu Dayan, Song Tao, Wang Shudong
College of Computer Science and Technology, China University of Petroleum (East China), Qingdao, 266580, Shandong, China.
Comput Struct Biotechnol J. 2024 Dec 4;23:4396-4405. doi: 10.1016/j.csbj.2024.11.050. eCollection 2024 Dec.
Accurate prediction of drug-target binding affinity remains a fundamental challenge in contemporary drug discovery. Despite significant advances in computational methods for protein-ligand binding affinity prediction, current approaches still face substantial limitations in prediction accuracy. Moreover, the prevalent methodologies often overlook critical three-dimensional (3D) structural information, thereby constraining their practical utility in computer-aided drug design (CADD). Here we present MM-DRPNet, a multimodal deep learning framework that enhances binding affinity prediction by integrating protein-ligand structural information with interaction features and physicochemical properties. The core innovation lies in our dynamic radial partitioning (DRP) algorithm, which adaptively segments 3D space based on complex-specific interaction patterns, surpassing traditional fixed partitioning methods in capturing spatial interactions. MM-DRPNet further incorporates molecular topological features to comprehensively model both structural and spatial relationships. Extensive evaluations on benchmark datasets demonstrate that MM-DRPNet significantly outperforms state-of-the-art methods across multiple metrics, with ablation studies confirming the substantial contribution of each architectural component. Source code for MM-DRPNet is freely available for download at https://github.com/Bigrock-dd/MMDRPv1.
准确预测药物与靶点的结合亲和力仍然是当代药物发现中的一项基本挑战。尽管在蛋白质-配体结合亲和力预测的计算方法方面取得了重大进展,但目前的方法在预测准确性方面仍面临重大限制。此外,普遍使用的方法往往忽略了关键的三维(3D)结构信息,从而限制了它们在计算机辅助药物设计(CADD)中的实际应用。在此,我们提出了MM-DRPNet,这是一个多模态深度学习框架,通过将蛋白质-配体结构信息与相互作用特征和物理化学性质相结合来增强结合亲和力预测。核心创新在于我们的动态径向分区(DRP)算法,该算法基于复合物特异性相互作用模式自适应地分割3D空间,在捕捉空间相互作用方面超越了传统的固定分区方法。MM-DRPNet进一步纳入了分子拓扑特征,以全面建模结构和空间关系。在基准数据集上的广泛评估表明,MM-DRPNet在多个指标上显著优于现有方法,消融研究证实了每个架构组件的重大贡献。MM-DRPNet的源代码可在https://github.com/Bigrock-dd/MMDRPv1上免费下载。