https://www.ncbi.nlm.nih.gov/pubmed/30716081
DeepDrug3D: Classification of ligand-binding pockets in proteins with a convolutional neural network.
Author information
- 1
- Division of Electrical & Computer Engineering, Louisiana State University, Baton Rouge, LA, United States of America.
- 2
- Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, United States of America.
- 3
- Division of Computer Science and Engineering, Louisiana State University, Baton Rouge, LA, United States of America.
- 4
- Center for Computation & Technology, Louisiana State University, Baton Rouge, LA, United States of America.
Abstract
Comprehensive characterization of ligand-binding sites is invaluable to infer molecular functions of hypothetical proteins, trace evolutionary relationships between proteins, engineer enzymes to achieve a desired substrate specificity, and develop drugs with improved selectivity profiles. These research efforts pose significant challenges owing to the fact that similar pockets are commonly observed across different folds, leading to the high degree of promiscuity of ligand-protein interactions at the system-level. On that account, novel algorithms to accurately classify binding sites are needed. Deep learning is attracting a significant attention due to its successful applications in a wide range of disciplines. In this communication, we present DeepDrug3D, a new approach to characterize and classify binding pockets in proteins with deep learning. It employs a state-of-the-art convolutional neural network in which biomolecular structures are represented as voxels assigned interaction energy-based attributes. The current implementation of DeepDrug3D, trained to detect and classify nucleotide- and heme-binding sites, not only achieves a high accuracy of 95%, but also has the ability to generalize to unseen data as demonstrated for steroid-binding proteins and peptidase enzymes. Interestingly, the analysis of strongly discriminative regions of binding pockets reveals that this high classification accuracy arises from learning the patterns of specific molecular interactions, such as hydrogen bonds, aromatic and hydrophobic contacts. DeepDrug3D is available as an open-source program at https://github.com/pulimeng/DeepDrug3D with the accompanying TOUGH-C1 benchmarking dataset accessible from https://osf.io/enz69/.
- PMID:
- 30716081
- PMCID:
- PMC6375647
- DOI:
- 10.1371/journal.pcbi.1006718
새로운 약물 개발,
핵심은 ligand, receptor 부위를 찾아내는 것.
3차원적인 구조를 CNN 으로 feature extraction 하여, 가능성이 놓은 약물을 만들어 내는 것
DeepDrug3D 라고 이름 지은.. 오픈 소프 프로그그램..
2019 PLosOne_ DeepDrug3D - Classification of ligand-binding.pdf
