Scalable N-Way Model Matching Using Multi-Dimensional Search Trees

Author(s):  
Alexander SchultheiB ◽  
Paul Maximilian Bittner ◽  
Lars Grunske ◽  
Thomas Thum ◽  
Timo Kehrer
Keyword(s):  
Author(s):  
Vikram Parthasarathy ◽  
Achuthan Raghava Menon ◽  
Basavaraj Devaranavadagi

Background: The anticancer properties of natural products calactin, calotropin and calotoxin are well established. However the mechanisms of their action are unclear and the molecular targets pertinent to them are not detailed. In this study, potential anti-cancer targets of these compounds have been identified using reverse screening approaches that may provide valuable insights into anti cancer drug development. Objective: To identify the potential anticancer targets of calactin, calotropin and calotoxin using reverse screening strategy. Methods: The ligands were screened for potential targets based on their shape similarity and pharmacophore model matching. The overlapping targets obtained from both methods were verified using reverse docking approach and validated by docking analysis. MM/PBSA calculation was performed to predict binding affinities between ligand and confirmed targets. Results: Interleukin-2 inducible T cell kinase [ITK] was confirmed as a potential target of calactin (Ki= -10.3 kcal/mol), calotropin (Ki= -8.7 kcal/mol) and calotoxin (Ki= -10.2 kcal/mol). The ligands interacted with hinge region residues such as Met438 and Asp500 which occupy the highly conserved ATP binding site. Binding energies of calactin (∆Ebind = -29.18 kJ/mol), calotropin (-28.57 kJ/mol) and calotoxin (-21.21 kJ/mol) with ITK were higher than (more negative) positive control sunitinib (-15.03 kJ/mol) and standard staurosporine (-21.09 kJ/mol). Besides this, Interstitial collagenase [MMP1] was confirmed as potential target of calotoxin (Ki= -8.2 kcal/mol).However the binding energy (∆Ebind = -11.89 kJ/mol) was lower compared to positive control batimastat (-21.07 kJ/mol). Conclusion: The results of this study confirmed ITK as a potential target for calactin, calotropin and calotoxin. These compounds can therefore be used as lead molecules for the development of novel ITK inhibitors, which may have immense therapeutic applications as immune-suppressants and as anticancer drugs.


Author(s):  
Dimitrios Siakavaras ◽  
Konstantinos Nikas ◽  
Georgios Goumas ◽  
Nectarios Koziris

2018 ◽  
Vol 53 (1) ◽  
pp. 207-218
Author(s):  
Dana Drachsler-Cohen ◽  
Martin Vechev ◽  
Eran Yahav
Keyword(s):  

Author(s):  
Mareike Fischer

AbstractTree balance plays an important role in different research areas like theoretical computer science and mathematical phylogenetics. For example, it has long been known that under the Yule model, a pure birth process, imbalanced trees are more likely than balanced ones. Also, concerning ordered search trees, more balanced ones allow for more efficient data structuring than imbalanced ones. Therefore, different methods to measure the balance of trees were introduced. The Sackin index is one of the most frequently used measures for this purpose. In many contexts, statements about the minimal and maximal values of this index have been discussed, but formal proofs have only been provided for some of them, and only in the context of ordered binary (search) trees, not for general rooted trees. Moreover, while the number of trees with maximal Sackin index as well as the number of trees with minimal Sackin index when the number of leaves is a power of 2 are relatively easy to understand, the number of trees with minimal Sackin index for all other numbers of leaves has been completely unknown. In this manuscript, we extend the findings on trees with minimal and maximal Sackin indices from the literature on ordered trees and subsequently use our results to provide formulas to explicitly calculate the numbers of such trees. We also extend previous studies by analyzing the case when the underlying trees need not be binary. Finally, we use our results to contribute both to the phylogenetic as well as the computer scientific literature using the new findings on Sackin minimal and maximal trees to derive formulas to calculate the number of both minimal and maximal phylogenetic trees as well as minimal and maximal ordered trees both in the binary and non-binary settings. All our results have been implemented in the Mathematica package SackinMinimizer, which has been made publicly available.


1975 ◽  
Vol 10 (3) ◽  
pp. 10-10
Author(s):  
R. Bayer ◽  
J. K. Metzger ◽  
München W. Germany
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document