DiPPI: Drugs in Protein-Protein Interaction Interfaces

2022-10
Cankara, Fatma
Şenyüz , Simge
Keskin , Özlem
Gürsoy , Attila
Protein-protein interactions (PPIs) modulation has been associated with various diseases. Proteins interact through their interfaces and interface characterization is important to understand the underlying mechanisms of the interaction. There has been an increasing interest in PPIs as drug targets, as analysis of binding regions and critical contacts may reveal more information about these mechanisms. Therefore, investigating the properties of the interactions is critical for the identification of drug targets, action mechanisms, and alternative pathways for drug repurposing. Here, we present a drug target dataset that can be utilized for drug repurposing studies with a focus on interface-bound drugs. Our dataset has two modules for drugs and interfaces. On the interface side, we extracted several properties of interfaces such as amino acid propensities, hotspots, evolutionary conservation of drug binding amino acids, and post-translational modifications of its residues. The interfaces are extracted from PDB and clustered based on their structural properties in our previous study. This broad characterization helps to identify similar interfaces with a focus on both physicochemical properties and structural similarity. On the drug side, we curated drug-like small molecules and FDA-approved drugs from various databases and created a subset that contains drugs bound to these interfaces. The drugs are clustered based on their molecular fingerprints to limit the search for an alternative drug to a smaller space. Drug properties such as following Lipinski’s rule and various molecular descriptors are also analyzed to further guide the selection of drug molecules. In total, we created a dataset consisting of 11,011 drug-like small molecules of which 343 are FDA-approved drugs. Filtered drug-like small molecules are found in 335,648 interfaces. 19,994 interfaces have an FDA-approved drug bound to them. Our highly redundant dataset provides users with an easy-to-follow scheme for drug repurposing studies through its well-curated and clustered interface and drug data.

Suggestions

PROT-ON: Structure-Based Detection of Critical Mutations in Redesigning Protein-Protein Interfaces
Koşaca, Mehdi; Yılmazbilek, İrem; Karaca , Ezgi (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10)
Deformation of protein-protein interactions (PPIs) causes several diseases. Many therapeutic agents have been developed by time-consuming experimental techniques. On the other hand, computational methods have been used to estimate the impact of interfacial mutations faster and more easily. The most used and accurate algorithms, EvoEF1 [1] and FoldX [2], are specialized to estimate the impact of mutations. However, their manual pipeline is insufficient to analyze all interfacial mutation possibilities. To ad...
Epileptic seizures induce structural and functional alterations on brain tissue membranes
Turker, Sevgi; Severcan, Mete; İLBAY, GÜL; Severcan, Feride (2014-12-01)
Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audio...
Association analysis of GSTT1, GSTM1 genotype polymorphisms and serum total GST activity with ischemic stroke risk
Turkanoglu, Aysun; Demirdogen, Birsen Can; Demirkaya, Seref; Bek, Semai; Adalı, Orhan (Springer Science and Business Media LLC, 2010-12-01)
Oxidative stress plays a major role in pathogenesis of atherosclerosis which is responsible for stroke. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. This study aimed to investigate the association of polymorphisms in GSTT1, GSTM1 genes and GST activity with ischemic stroke risk. Patients had almost the same GST activity as that of controls. No significant differences were found between patients and controls in terms...
Integromic Analysis of Genetic Variation and Gene Expression Identifies Networks for Cardiovascular Disease Phenotypes
Yao, Chen; Chen, Brian H.; Joehanes, Roby; Otlu, Burcak; Zhang, Xiaoling; Liu, Chunyu; Huan, Tianxiao; Tastan, Oznur; Cupples, L. Adrienne; Meigs, James B.; Fox, Caroline S.; Freedman, Jane E.; Courchesne, Paul; O'Donnell, Christopher J.; Munson, Peter J.; Keles, Sunduz; Levy, Daniel (Ovid Technologies (Wolters Kluwer Health), 2015-02-10)
Background-Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown.
Comparison of fluorescent protein labelled and wild type NMDA receptor distribution
Pirinçci, Şerife Şeyda; Son, Çağdaş Devrim; Department of Biology (2013)
NMDA (N-methyl D-aspartate) Receptor is a ligand and voltage gated ion channel and involved in many processes such as synaptic plasticity, memory formation, behavioral responses and cell survival. In the sense of functional activity, cellular localization of NMDAR is important since this receptor shows its activity on the membrane. Although NMDA receptor is intensely studied there are no satisfying study showing its localization with microscobic methods. Besides, the effect of florescent protein labelling o...
Citation Formats
F. Cankara, S. Şenyüz, Ö. Keskin, and A. Gürsoy, “DiPPI: Drugs in Protein-Protein Interaction Interfaces,” Erdemli, Mersin, TÜRKİYE, 2022, p. 3100, Accessed: 00, 2023. [Online]. Available: https://hibit2022.ims.metu.edu.tr/.