ChemInform Abstract: Identification and Mapping of Small-Molecule Binding Sites in Proteins: Computational Tools for Structure-Based Drug Design.

ChemInform ◽  
2010 ◽  
Vol 33 (47) ◽  
pp. no-no
Author(s):  
Christoph Sotriffer ◽  
Gerhard Klebe
Keyword(s):  
Drug Design ◽  
Small Molecule ◽  
Binding Sites ◽  
Computational Tools ◽  
Structure Based Drug Design

3D U-Net: A voxel-based method in binding site prediction of protein structure

2021 ◽  
Vol 19 (02) ◽  
pp. 2150006
Author(s):  
Fatemeh Nazem ◽  
Fahimeh Ghasemi ◽  
Afshin Fassihi ◽  
Alireza Mehri Dehnavi
Keyword(s):  
Drug Design ◽  
Binding Site ◽  
Binding Sites ◽  
Semantic Segmentation ◽  
Structure Based Drug Design ◽  
Site Prediction ◽  
Binding Site Prediction ◽  
Novel Proteins ◽  
Proposed Model ◽  
Deep Learning Model

Binding site prediction for new proteins is important in structure-based drug design. The identified binding sites may be helpful in the development of treatments for new viral outbreaks in the world when there is no information available about their pockets with COVID-19 being a case in point. Identification of the pockets using computational methods, as an alternative method, has recently attracted much interest. In this study, the binding site prediction is viewed as a semantic segmentation problem. An improved 3D version of the U-Net model based on the dice loss function is utilized to predict the binding sites accurately. The performance of the proposed model on the independent test datasets and SARS-COV-2 shows the segmentation model could predict the binding sites with a more accurate shape than the recently published deep learning model, i.e. DeepSite. Therefore, the model may help predict the binding sites of proteins and could be used in drug design for novel proteins.

Computational Tools for Structure Based Drug Design

1998 ◽  
pp. 239-247
Author(s):  
Benjamin J. Burke ◽  
Xinjun Hou ◽  
Thomas F. Hendrickson
Keyword(s):  
Drug Design ◽  
Computational Tools ◽  
Structure Based Drug Design

scholarly journals Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939

2012 ◽  
Vol 68 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Christina A. Kirby ◽  
Atwood Cheung ◽  
Aleem Fazal ◽  
Michael D. Shultz ◽  
Travis Stams
Keyword(s):  
Drug Design ◽  
Crystal Structures ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Donor Site ◽  
Structure Based Drug Design ◽  
Crystallization System ◽  
Tankyrase 1

The crystal structures of tankyrase 1 (TNKS1) in complex with two small-molecule inhibitors, PJ34 and XAV939, both at 2.0 Å resolution, are reported. The structure of TNKS1 in complex with PJ34 reveals two molecules of PJ34 bound in the NAD+donor pocket. One molecule is in the nicotinamide portion of the pocket, as previously observed in other PARP structures, while the second molecule is bound in the adenosine portion of the pocket. Additionally, unlike the unliganded crystallization system, the TNKS1–PJ34 crystallization system has the NAD+donor site accessible to bulk solvent in the crystal, which allows displacement soaking. The TNKS1–PJ34 crystallization system was used to determine the structure of TNKS1 in complex with XAV939. These structures provide a basis for the start of a structure-based drug-design campaign for TNKS1.

Rational Drug Design

2014 ◽  
Vol 4 (1) ◽  
pp. 59-85 ◽  
Author(s):  
Khaled H. Barakat ◽  
Michael Houghton ◽  
D. Lorne Tyrrel ◽  
Jack A. Tuszynski
Keyword(s):  
Drug Design ◽  
Rational Drug Design ◽  
Dimensional Structure ◽  
Computational Tools ◽  
Structure Based Drug Design ◽  
Practical Applications ◽  
3 Dimensional ◽  
Drug Candidates ◽  
The Past ◽  
Rational Drug

For the past three decades rationale drug design (RDD) has been developing as an innovative, rapid and successful way to discover new drug candidates. Many strategies have been followed and several targets with diverse structures and different biological roles have been investigated. Despite the variety of computational tools available, one can broadly divide them into two major classes that can be adopted either separately or in combination. The first class involves structure-based drug design, when the target's 3-dimensional structure is available or it can be computationally generated using homology modeling. On the other hand, when only a set of active molecules is available, and the structure of the target is unknown, ligand-based drug design tools are usually used. This review describes some recent advances in rational drug design, summarizes a number of their practical applications, and discusses both the advantages and shortcomings of the various techniques used.

Structure-based Drug Design Strategies in the Development of Small Molecule Inhibitors Targeting Bcl-2 Family Proteins

2020 ◽  
Vol 17 (8) ◽  
pp. 943-953
Author(s):  
Zhe Yin ◽  
Donglin Yang ◽  
Jun Wang ◽  
Yuequan Jiang
Keyword(s):  
Clinical Trials ◽  
Drug Design ◽  
B Cell ◽  
Cancer Cells ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Design Strategies ◽  
Structure Based Drug Design

Proteins of B-cell lymphoma (Bcl-2) family are key regulators of apoptosis and are involved in the pathogenesis of various cancers. Disrupting the interactions between the antiapoptotic and proapoptotic Bcl-2 members is an attractive strategy to reactivate the apoptosis of cancer cells. Structure-based drug design (SBDD) has been successfully applied to the discovery of small molecule inhibitors targeting Bcl-2 proteins in past decades. Up to now, many Bcl-2 inhibitors with different paralogue selectivity profiles have been developed and some were used in clinical trials. This review focused on the recent applications of SBDD strategies in the development of small molecule inhibitors targeting Bcl-2 family proteins.

Towards structure-based protein drug design

2011 ◽  
Vol 39 (5) ◽  
pp. 1382-1386 ◽  
Author(s):  
Changsheng Zhang ◽  
Luhua Lai
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Small Molecule ◽  
Protein Interactions ◽  
De Novo ◽  
Protein Docking ◽  
Erythropoietin Receptor ◽  
Protein Drug ◽  
Protein Protein Interactions ◽  
Structure Based Drug Design

Structure-based drug design for chemical molecules has been widely used in drug discovery in the last 30 years. Many successful applications have been reported, especially in the field of virtual screening based on molecular docking. Recently, there has been much progress in fragment-based as well as de novo drug discovery. As many protein–protein interactions can be used as key targets for drug design, one of the solutions is to design protein drugs based directly on the protein complexes or the target structure. Compared with protein–ligand interactions, protein–protein interactions are more complicated and present more challenges for design. Over the last decade, both sampling efficiency and scoring accuracy of protein–protein docking have increased significantly. We have developed several strategies for structure-based protein drug design. A grafting strategy for key interaction residues has been developed and successfully applied in designing erythropoietin receptor-binding proteins. Similarly to small-molecule design, we also tested de novo protein-binder design and a virtual screen of protein binders using protein–protein docking calculations. In comparison with the development of structure-based small-molecule drug design, we believe that structure-based protein drug design has come of age.

Structure-based drug design of small molecule SIRT1 modulators to treat cancer and metabolic disorders

2014 ◽  
Vol 52 ◽  
pp. 46-56 ◽  
Author(s):  
Venkat Koushik Pulla ◽  
Mallika Alvala ◽  
Dinavahi Saketh Sriram ◽  
Srikant Viswanadha ◽  
Dharmarajan Sriram ◽  
...  
Keyword(s):  
Drug Design ◽  
Small Molecule ◽  
Metabolic Disorders ◽  
Structure Based Drug Design
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