Complex Network Spectral Moments for ATCUN Motif DNA Cleavage: First Predictive Study on Proteins of Human Pathogen Parasites

Abstract

The development of methods that can predict the metal-mediated biological activity based only on the 3D structure of metal-unbound proteins has become a goal of major importance. This work is dedicated to the amino terminal Cu(II)- and Ni(II)-binding (ATCUN) motifs that participate in the DNA cleavage and have antitumor activity. We have calculated herein, for the first time, the 3D electrostatic spectral moments for 415 different proteins, including 133 potential ATCUN antitumor proteins. Using these parameters as input for Linear Discriminant Analysis, we have found a model that discriminates between ATCUN-DNA cleavage proteins and nonactive proteins with 91.32% Accuracy (379 out of 415 of proteins including both training and external validation series). Finally, the model has predicted for the first time the DNA cleavage function of proteins from the pathogen parasites. We have predicted possible ATCUN-like proteins with a probability higher than 99% in nine parasite families such as Trypanosoma, Plasmodium, Leishmania, or Toxoplasma. The distribution by biological function of the ATCUN proteins predicted has been the following: oxidoreductases 70.5%, signaling proteins 62.5%, lyases 58.2%, membrane proteins 45.5%, ligases 44.4%, hydrolases 41.3%, transferases 39.2%, cell adhesion proteins 34.5%, metal binders 33.5%, translation proteins 25.0%, transporters 16.7%, structural proteins 9.1%, and isomerases 8.2%. The model is implemented at http://miaja.tic.udc.es/Bio-AIMS/ATCUNPred.php.

Drastic Effect of the Peptide Sequence on the Copper‐Binding Properties of Tripeptides and the Electrochemical Behaviour of Their Copper(II) Complexes

“…The computed reduction potential fort he ATCUN-like complex ( Figure S6, Supporting Information) is À1.35 V, whereas that for the 3N1O complex ( Figure 6), with only one deprotonated amide, is À0.23 V. The data for the latter complex is in very good agreement with the value of À0.24 Vo bserved by CV for the one-electron reduction peak E pc .T hus, these results suggest that, in order to achieve the ATCUN like coordination with two deprotonateda mides,t he binding of two consecutive five-membered rings is necessary to provide the required stabilization, so as the coordination of the amino-terminal group. This is similar to that found for 3N1O Cu II -Ab (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), for which molecular dynamics simulations indicated that CO decoordination occurs rapidly at t = 0.2 ps. That is, the initial distorted square-planar (3 N1O) coordination geometry of the Cu II -Ac-HWH complex changes to at rigonal-planar molecular geometry (Figure 8), in which the copper interacts with three nitrogen atoms( 3N).…”

“…[44,54,55] For instance, for Cu II -Ab (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), with aH is residue in the third position, the CV indicates that the complex does not yield any electrochemical Cu II /Cu I redox activity due to the formation of an ATCUN binding mode. [44,54,55] For instance, for Cu II -Ab (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), with aH is residue in the third position, the CV indicates that the complex does not yield any electrochemical Cu II /Cu I redox activity due to the formation of an ATCUN binding mode.…”

iLoc-Euk: A Multi-Label Classifier for Predicting the Subcellular Localization of Singleplex and Multiplex Eukaryotic Proteins

“…Facing the avalanche of protein sequences generated in the post-genomic age, it is highly desired to develop computational methods for timely and effectively identifying various biological features for newly found proteins [5], [6], [7], [8], particularly to develop user-friendly web-servers in this regard [9], [10]. In this study, we are to focus on the topic of protein subcellular localization.…”

QSAR Models for Proteins of Parasitic Organisms, Plants and Human Guests: Theory, Applications, Legal Protection, Taxes, and Regulatory Issues

“…The model predicts possible AT-CUN proteins in some parasite organisms. However, there is currently few experimental evidence on the existence of ATCUN proteins in human pathogen parasites [108].…”