HTML Microdata document

This HTML5 document contains 551 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

Prefix	IRI
bibo	http://purl.org/ontology/bibo/
rdf	http://www.w3.org/1999/02/22-rdf-syntax-ns#
n3	http://purl.jp/bio/10/colil/ontology/201303#
n10	http://dx.doi.org/
n4	http://purl.jp/bio/10/colil/id/
n8	http://pubannotation.org/docs/sourcedb/PMC/sourceid/
n2	http://purl.org/spar/doco/
rdfs	http://www.w3.org/2000/01/rdf-schema#
dc	http://purl.org/dc/elements/1.1/
n11	http://togows.dbcls.jp/entry/pubmed/
n9	http://www.ncbi.nlm.nih.gov/pmc/articles/
xsdh	http://www.w3.org/2001/XMLSchema#

Statements

Subject Item: n4:23272099
rdf:type: n3:CitationPaper n3:RelevantPaper n3:ReferencePaper
rdfs:seeAlso: n8:0 n9:0 n10:10.1371%2Fjournal.pone.0051329 n11:23272099
bibo:cites: n4:19186108 n4:11470599 n4:15055986 n4:11790605 n4:19399780 n4:19153657 n4:15116359 n4:18594541 n4:17488841 n4:11543671 n4:16200636 n4:20527952 n4:4795686 n4:11123888 n4:20659685 n4:9440758 n4:15095299 n4:10675030 n4:20863882 n4:20427241 n4:19473860 n4:16981200 n4:16093443 n4:7675086 n4:17948053 n4:11212280 n4:19805003 n4:686623 n4:10493501 n4:12579579 n4:17176115 n4:18367095 n4:18981420 n4:8451640 n4:20056466 n4:10074455 n4:20647037 n4:10373009 n4:17606717 n4:10517972 n4:12010024 n4:17229776
n3:cocitationWith: n4:30386247 n4:9722633 n4:18256616 n4:25268380 n4:17882165 n4:26939044 n4:24474685 n4:15055986 n4:11008124 n4:21892204 n4:19153606 n4:10810335 n4:19023283 n4:20846399 n4:31906898 n4:10463593 n4:26321360 n4:23580445 n4:23807173 n4:10592235 n4:19332554 n4:12915808 n4:25956741 n4:9440758 n4:22261329 n4:27650543 n4:21701511 n4:30208165 n4:12580598 n4:15095299 n4:18343204 n4:22941649 n4:23178497 n4:26318993 n4:17948053 n4:14576837 n4:21034966 n4:7891694 n4:20662484 n4:10493501 n4:28541665 n4:31369707 n4:16957145 n4:27247238 n4:16076955 n4:12679022 n4:22562137 n4:9052754 n4:17183314 n4:10074455 n4:20418188
n3:hasRelevantBibliographicResourceOf: _:vb511093493 _:vb511093494 _:vb511093495 _:vb511093500 _:vb511093501 _:vb511093502 _:vb511093503 _:vb511093496 _:vb511093497 _:vb511093498 _:vb511093499 _:vb511093524 _:vb511093525 _:vb511093526 _:vb511093527 _:vb511093520 _:vb511093521 _:vb511093522 _:vb511093523 _:vb511093532 _:vb511093533 _:vb511093534 _:vb511093535 _:vb511093528 _:vb511093529 _:vb511093530 _:vb511093531 _:vb511093508 _:vb511093509 _:vb511093510 _:vb511093511 _:vb511093504 _:vb511093505 _:vb511093506 _:vb511093507 _:vb511093516 _:vb511093517 _:vb511093518 _:vb511093519 _:vb511093512 _:vb511093513 _:vb511093514 _:vb511093515 _:vb511093540 _:vb511093541 _:vb511093542 _:vb511093543 _:vb511093536 _:vb511093537 _:vb511093538 _:vb511093539
n3:pmcid: PMC0
bibo:doi: 10.1371%2Fjournal.pone.0051329
n2:contains: _:vb19902414 _:vb19902433 _:vb19902447

Subject Item: _:vb19902414
rdf:type: n2:Section
dc:title: introduction
n2:contains: _:vb19902428 _:vb19902429 _:vb19902430 _:vb19902431 _:vb19902424 _:vb19902425 _:vb19902426 _:vb19902427 _:vb19902420 _:vb19902421 _:vb19902422 _:vb19902423 _:vb19902416 _:vb19902417 _:vb19902418 _:vb19902419 _:vb19902415 _:vb19902432

Subject Item: _:vb19902415
rdf:type: n3:Context
rdf:value: In normal cells, NER removes many types of DNA lesions, protecting cell integrity [>>1<<]. However, in cancer cells exposed to DNA damaging agents that distort the DNA helix or form bulky injuries to the genome, NER comes into play and removes the damage, thus protecting cancer cells from death [1], [2]. A striking example of
n3:mentions: n4:20863882

Subject Item: _:vb19902416
rdf:type: n3:Context
rdf:value: However, in cancer cells exposed to DNA damaging agents that distort the DNA helix or form bulky injuries to the genome, NER comes into play and removes the damage, thus protecting cancer cells from death [>>1<<], [2]. A striking example of this mechanism is represented by the use of platinum compounds such as cisplatin, the backbone for many treatments of solid tumors including testicular, bladder, ovarian, head and neck, cervical, lung and
n3:mentions: n4:20863882

Subject Item: _:vb19902417
rdf:type: n3:Context
rdf:value: However, in cancer cells exposed to DNA damaging agents that distort the DNA helix or form bulky injuries to the genome, NER comes into play and removes the damage, thus protecting cancer cells from death [1], [>>2<<]. A striking example of this mechanism is represented by the use of platinum compounds such as cisplatin, the backbone for many treatments of solid tumors including testicular, bladder, ovarian, head and neck, cervical, lung and colorectal
n3:mentions: n4:19153657

Subject Item: _:vb19902418
rdf:type: n3:Context
rdf:value: example of this mechanism is represented by the use of platinum compounds such as cisplatin, the backbone for many treatments of solid tumors including testicular, bladder, ovarian, head and neck, cervical, lung and colorectal cancer [>>3<<]. It has been demonstrated that NER is the major DNA repair mechanism that removes cisplatin-induced DNA damage, and that resistance to platinum-based therapy correlates with high expression of ERCC1, a major element of the NER machinery
n3:mentions: n4:20647037

Subject Item: _:vb19902419
rdf:type: n3:Context
rdf:value: It has been demonstrated that NER is the major DNA repair mechanism that removes cisplatin-induced DNA damage, and that resistance to platinum-based therapy correlates with high expression of ERCC1, a major element of the NER machinery [>>4<<], [5], [6], [7]. In this context, one way to increase the efficacy of platinum therapy and decrease drug resistance is to regulate NER by inhibiting the activity of ERCC1 and interacting proteins using novel therapeutic compounds [8].
n3:mentions: n4:9440758

Subject Item: _:vb19902420
rdf:type: n3:Context
rdf:value: been demonstrated that NER is the major DNA repair mechanism that removes cisplatin-induced DNA damage, and that resistance to platinum-based therapy correlates with high expression of ERCC1, a major element of the NER machinery [4], [>>5<<], [6], [7]. In this context, one way to increase the efficacy of platinum therapy and decrease drug resistance is to regulate NER by inhibiting the activity of ERCC1 and interacting proteins using novel therapeutic compounds [8].
n3:mentions: n4:17606717

Subject Item: _:vb19902421
rdf:type: n3:Context
rdf:value: demonstrated that NER is the major DNA repair mechanism that removes cisplatin-induced DNA damage, and that resistance to platinum-based therapy correlates with high expression of ERCC1, a major element of the NER machinery [4], [5], [>>6<<], [7]. In this context, one way to increase the efficacy of platinum therapy and decrease drug resistance is to regulate NER by inhibiting the activity of ERCC1 and interacting proteins using novel therapeutic compounds [8].
n3:mentions: n4:17229776

Subject Item: _:vb19902422
rdf:type: n3:Context
rdf:value: that NER is the major DNA repair mechanism that removes cisplatin-induced DNA damage, and that resistance to platinum-based therapy correlates with high expression of ERCC1, a major element of the NER machinery [4], [5], [6], [>>7<<]. In this context, one way to increase the efficacy of platinum therapy and decrease drug resistance is to regulate NER by inhibiting the activity of ERCC1 and interacting proteins using novel therapeutic compounds [8].
n3:mentions: n4:18594541

Subject Item: _:vb19902423
rdf:type: n3:Context
rdf:value: In this context, one way to increase the efficacy of platinum therapy and decrease drug resistance is to regulate NER by inhibiting the activity of ERCC1 and interacting proteins using novel therapeutic compounds [>>8<<].
n3:mentions: n4:19805003

Subject Item: _:vb19902424
rdf:type: n3:Context
rdf:value: The protein ERCC1 forms a heterodimer with XPF. The resulting complex is an endonuclease enzyme that cleaves the 5` end of the damage whereas XPG cleaves in the 3′ position (for a comprehensive review on NER, see ref. [>>2<<]). ERCC1-XPF is recruited to the damage site through a direct interaction between the centeral domain of ERCC1 and XPA, an indispensible element of the NER pathways [9], [10].
n3:mentions: n4:19153657

Subject Item: _:vb19902425
rdf:type: n3:Context
rdf:value: ERCC1-XPF is recruited to the damage site through a direct interaction between the centeral domain of ERCC1 and XPA, an indispensible element of the NER pathways [>>9<<], [10]. No cellular function beyond NER has been observed for XPA and competitive inhibition of the XPA interaction with peptide fragments is effective at disrupting NER [11], [12]. Furthermore, clinically, patients that have been shown to
n3:mentions: n4:17176115

Subject Item: _:vb19902426
rdf:type: n3:Context
rdf:value: ERCC1-XPF is recruited to the damage site through a direct interaction between the centeral domain of ERCC1 and XPA, an indispensible element of the NER pathways [9], [>>10<<]. No cellular function beyond NER has been observed for XPA and competitive inhibition of the XPA interaction with peptide fragments is effective at disrupting NER [11], [12]. Furthermore, clinically, patients that have been shown to have
n3:mentions: n4:10675030

Subject Item: _:vb19902427
rdf:type: n3:Context
rdf:value: No cellular function beyond NER has been observed for XPA and competitive inhibition of the XPA interaction with peptide fragments is effective at disrupting NER [>>11<<], [12]. Furthermore, clinically, patients that have been shown to have low expression levels of either XPA or ERCC1 demonstrate higher sensitivity to cisplatin treatment, and people deficient for XPA (or other XP proteins) are
n3:mentions: n4:11212280

Subject Item: _:vb19902428
rdf:type: n3:Context
rdf:value: No cellular function beyond NER has been observed for XPA and competitive inhibition of the XPA interaction with peptide fragments is effective at disrupting NER [11], [>>12<<]. Furthermore, clinically, patients that have been shown to have low expression levels of either XPA or ERCC1 demonstrate higher sensitivity to cisplatin treatment, and people deficient for XPA (or other XP proteins) are hypersensitive to
n3:mentions: n4:17948053

Subject Item: _:vb19902429
rdf:type: n3:Context
rdf:value: patients that have been shown to have low expression levels of either XPA or ERCC1 demonstrate higher sensitivity to cisplatin treatment, and people deficient for XPA (or other XP proteins) are hypersensitive to UV radiations [>>13<<], [14]. Hence, here we continue our earlier efforts aimed at the identification and characterization of novel inhibitors of the interaction between ERCC1 and XPA [15], in order to regulate the NER pathway and offer new alternatives to be
n3:mentions: n4:10074455

Subject Item: _:vb19902430
rdf:type: n3:Context
rdf:value: patients that have been shown to have low expression levels of either XPA or ERCC1 demonstrate higher sensitivity to cisplatin treatment, and people deficient for XPA (or other XP proteins) are hypersensitive to UV radiations [13], [>>14<<]. Hence, here we continue our earlier efforts aimed at the identification and characterization of novel inhibitors of the interaction between ERCC1 and XPA [15], in order to regulate the NER pathway and offer new alternatives to be added
n3:mentions: n4:15095299

Subject Item: _:vb19902431
rdf:type: n3:Context
rdf:value: Hence, here we continue our earlier efforts aimed at the identification and characterization of novel inhibitors of the interaction between ERCC1 and XPA [>>15<<], in order to regulate the NER pathway and offer new alternatives to be added to the current NER and cell cycle inhibitor UCN-01(7-hydroxystaurosporine) [16].
n3:mentions: n4:19473860

Subject Item: _:vb19902432
rdf:type: n3:Context
rdf:value: characterization of novel inhibitors of the interaction between ERCC1 and XPA [15], in order to regulate the NER pathway and offer new alternatives to be added to the current NER and cell cycle inhibitor UCN-01(7-hydroxystaurosporine) [>>16<<]. The present work introduces a promising lead compound NERI01 (NER inhibitor 01) that targets the ERCC1-XPA interaction and sensitizes cancer cells to ultraviolet irradiation induced damage.
n3:mentions: n4:10493501

Subject Item: _:vb19902433
rdf:type: n2:Section
dc:title: materials and methods
n2:contains: _:vb19902434 _:vb19902435 _:vb19902436 _:vb19902437 _:vb19902438 _:vb19902439 _:vb19902440 _:vb19902441 _:vb19902442 _:vb19902443 _:vb19902444 _:vb19902445 _:vb19902446

Subject Item: _:vb19902434
rdf:type: n3:Context
rdf:value: Our next step relied on Tsodikov’s NMR crystal structure of XPA bound to ERCC1 (PDB entry 2JNW) [>>12<<]. The NMR ensemble included 10 different conformations for the proteins; all of them were used in this study.
n3:mentions: n4:17948053

Subject Item: _:vb19902435
rdf:type: n3:Context
rdf:value: The binding site was characterized in our previous work (see Figure 2) [>>15<<]. In this model, the central domain of ERCC1 (residues 99–214) is bound to a fragment of XPA (residues 67–77).
n3:mentions: n4:19473860

Subject Item: _:vb19902436
rdf:type: n3:Context
rdf:value: Prior to docking, the XPA peptide was removed, protonation states of the residues constituting the ERCC1 pocket were adjusted using the software PDB2PQR [>>45<<], and the protein structures were conformationally relaxed using the NAMD molecular dynamics software with constraints on the backbone atoms (see below).
n3:mentions: n4:17488841

Subject Item: _:vb19902437
rdf:type: n3:Context
rdf:value: All docking simulations employed the software AutoDock, version 4.0 [>>46<<]. The docking method and parameters were similar to the ones used in our previous work [15].
n3:mentions: n4:19399780

Subject Item: _:vb19902438
rdf:type: n3:Context
rdf:value: The docking method and parameters were similar to the ones used in our previous work [>>15<<]. The screening method adopted two filtering phases with the same docking parameters. First, we screened the entire CN library against a single target model followed by applying the relaxed complex scheme (RCS) [47] through docking of the
n3:mentions: n4:19473860

Subject Item: _:vb19902439
rdf:type: n3:Context
rdf:value: First, we screened the entire CN library against a single target model followed by applying the relaxed complex scheme (RCS) [>>47<<] through docking of the top 2,000 hits from the first screen against the rest of the ten target structures (see results for more details).
n3:mentions: n4:12010024

Subject Item: _:vb19902440
rdf:type: n3:Context
rdf:value: Clustering of the docking results followed the same adaptive procedure as the one employed in our previous study [>>15<<]. In brief, for each docking simulation a modified version of the PTRAJ module of AMBER [48] clustered the docking trials.
n3:mentions: n4:19473860

Subject Item: _:vb19902441
rdf:type: n3:Context
rdf:value: In brief, for each docking simulation a modified version of the PTRAJ module of AMBER [>>48<<] clustered the docking trials.
n3:mentions: n4:16200636

Subject Item: _:vb19902442
rdf:type: n3:Context
rdf:value: The AMBER99SB force field [>>50<<] was used for protein parameterization, while the generalized AMBER force field (GAFF) provided parameters for ligands [51].
n3:mentions: n4:16981200

Subject Item: _:vb19902443
rdf:type: n3:Context
rdf:value: The AMBER99SB force field [50] was used for protein parameterization, while the generalized AMBER force field (GAFF) provided parameters for ligands [>>51<<]. For each ligand, partial charges were calculated with the AM1-BCC method using the Antechamber module of AMBER 10. Protonation states of all ionizable residues were calculated using the program PDB2PQR. All simulations were performed at
n3:mentions: n4:15116359

Subject Item: _:vb19902444
rdf:type: n3:Context
rdf:value: This study utilized the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) technique to rescore the preliminary ranked docking hits [>>32<<]. It combines molecular mechanics with continuum solvation models.
n3:mentions: n4:11123888

Subject Item: _:vb19902445
rdf:type: n3:Context
rdf:value: Most compounds have not been reported elsewhere, but the synthesis of AB-00005094 [>>54<<], AB-00012818 and AB-00012800 [55], [56] have previously been published.
n3:mentions: n4:686623

Subject Item: _:vb19902446
rdf:type: n3:Context
rdf:value: Media with or without potential inhibitors was added and cells were incubated for another 72 hours before living cells were quantified with methylthiazoletetrazolium (MTT) assay as previously described [>>57<<].
n3:mentions: n4:16093443

Subject Item: _:vb19902447
rdf:type: n2:Section
dc:title: results and discussion
n2:contains: _:vb19902466 _:vb19902467 _:vb19902468 _:vb19902469 _:vb19902470 _:vb19902471 _:vb19902456 _:vb19902457 _:vb19902458 _:vb19902459 _:vb19902460 _:vb19902461 _:vb19902462 _:vb19902463 _:vb19902448 _:vb19902449 _:vb19902450 _:vb19902451 _:vb19902452 _:vb19902453 _:vb19902454 _:vb19902455 _:vb19902472 _:vb19902473 _:vb19902474 _:vb19902475 _:vb19902464 _:vb19902465

Subject Item: _:vb19902448
rdf:type: n3:Context
rdf:value: For example, Philippopoulos et al. suggested NMR structures as the most effective source for protein conformations [>>20<<]. A set of 15 NMR conformations for ribonuclease HI was compared to a trajectory obtained from a 1.7 ns MD simulation. The NMR data explored the conformational space of the protein more efficiently than the conventional MD simulation. In
n3:mentions: n4:10373009

Subject Item: _:vb19902449
rdf:type: n3:Context
rdf:value: In our present work, we exploited the published ERCC1-XPA NMR structure [>>12<<]. However, as the initial screening involved an enormous number of compounds (∼ 90,000) (see below), it was important to start the docking simulations using a representative target structure.
n3:mentions: n4:17948053

Subject Item: _:vb19902450
rdf:type: n3:Context
rdf:value: The second stage was a more rigorous docking approach that employed the RCS methodology [>>21<<]. In the RCS approach, all-atom MD simulations (e.g., 2–5 ns simulation) are applied to explore the conformational space of the target, while docking is subsequently used for the fast screening of drug libraries against an ensemble of
n3:mentions: n4:12579579

Subject Item: _:vb19902451
rdf:type: n3:Context
rdf:value: An excellent example is that of an HIV inhibitor, raltegravir which became the first FDA approved drug targeting HIV integrase [>>22<<], [23]. Other successful examples include the identification of novel inhibitors of the acetylcholine binding protein [24], RNA-editing ligase 1 [25], the influenza protein neuraminidase [26] and Trypanosoma brucei uridine diphosphate
n3:mentions: n4:15055986

Subject Item: _:vb19902452
rdf:type: n3:Context
rdf:value: Other successful examples include the identification of novel inhibitors of the acetylcholine binding protein [>>24<<], RNA-editing ligase 1 [25], the influenza protein neuraminidase [26] and Trypanosoma brucei uridine diphosphate galactose 4′-epimerase [27].
n3:mentions: n4:19186108

Subject Item: _:vb19902453
rdf:type: n3:Context
rdf:value: Other successful examples include the identification of novel inhibitors of the acetylcholine binding protein [24], RNA-editing ligase 1 [>>25<<], the influenza protein neuraminidase [26] and Trypanosoma brucei uridine diphosphate galactose 4′-epimerase [27].
n3:mentions: n4:18981420

Subject Item: _:vb19902454
rdf:type: n3:Context
rdf:value: Other successful examples include the identification of novel inhibitors of the acetylcholine binding protein [24], RNA-editing ligase 1 [25], the influenza protein neuraminidase [>>26<<] and Trypanosoma brucei uridine diphosphate galactose 4′-epimerase [27].
n3:mentions: n4:20427241

Subject Item: _:vb19902455
rdf:type: n3:Context
rdf:value: examples include the identification of novel inhibitors of the acetylcholine binding protein [24], RNA-editing ligase 1 [25], the influenza protein neuraminidase [26] and Trypanosoma brucei uridine diphosphate galactose 4′-epimerase [>>27<<]. These applications employed alternative ways to solve two main problems with the method, namely, reducing the number of extracted target conformations and deciding on how to select the final set of hits after carrying out the screening
n3:mentions: n4:20527952

Subject Item: _:vb19902456
rdf:type: n3:Context
rdf:value: For the first problem, a number of studies suggested extracting the structures at larger intervals of the MD simulation (e.g. every 5 ns or so), [>>24<<] condensing the structural ensemble generated from MD simulations using QR factorization, [25] or clustering the MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [26], [27] On the other hand, to rank the
n3:mentions: n4:19186108

Subject Item: _:vb19902457
rdf:type: n3:Context
rdf:value: the first problem, a number of studies suggested extracting the structures at larger intervals of the MD simulation (e.g. every 5 ns or so), [24] condensing the structural ensemble generated from MD simulations using QR factorization, [>>25<<] or clustering the MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [26], [27] On the other hand, to rank the screened compounds and suggest a final set of top hits, some studies used only docking
n3:mentions: n4:18981420

Subject Item: _:vb19902458
rdf:type: n3:Context
rdf:value: simulation (e.g. every 5 ns or so), [24] condensing the structural ensemble generated from MD simulations using QR factorization, [25] or clustering the MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [>>26<<], [27] On the other hand, to rank the screened compounds and suggest a final set of top hits, some studies used only docking predictions, [24], [25], [26]while others suggested (as in this thesis) using a more accurate scoring method (e.g.
n3:mentions: n4:20427241

Subject Item: _:vb19902459
rdf:type: n3:Context
rdf:value: (e.g. every 5 ns or so), [24] condensing the structural ensemble generated from MD simulations using QR factorization, [25] or clustering the MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [26], [>>27<<] On the other hand, to rank the screened compounds and suggest a final set of top hits, some studies used only docking predictions, [24], [25], [26]while others suggested (as in this thesis) using a more accurate scoring method (e.g.
n3:mentions: n4:20527952

Subject Item: _:vb19902460
rdf:type: n3:Context
rdf:value: the MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [26], [27] On the other hand, to rank the screened compounds and suggest a final set of top hits, some studies used only docking predictions, [>>24<<], [25], [26]while others suggested (as in this thesis) using a more accurate scoring method (e.g. MM/PBSA (Molecular Mechanics/Poisson Boltzmann Surface Area)) to refine the final selected hits.
n3:mentions: n4:19186108

Subject Item: _:vb19902461
rdf:type: n3:Context
rdf:value: the MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [26], [27] On the other hand, to rank the screened compounds and suggest a final set of top hits, some studies used only docking predictions, [24], [>>25<<], [26]while others suggested (as in this thesis) using a more accurate scoring method (e.g. MM/PBSA (Molecular Mechanics/Poisson Boltzmann Surface Area)) to refine the final selected hits.
n3:mentions: n4:18981420

Subject Item: _:vb19902462
rdf:type: n3:Context
rdf:value: MD trajectory using root-mean-square-deviation (RMSD) conformational clustering, [26], [27] On the other hand, to rank the screened compounds and suggest a final set of top hits, some studies used only docking predictions, [24], [25], [>>26<<]while others suggested (as in this thesis) using a more accurate scoring method (e.g. MM/PBSA (Molecular Mechanics/Poisson Boltzmann Surface Area)) to refine the final selected hits.
n3:mentions: n4:20427241

Subject Item: _:vb19902463
rdf:type: n3:Context
rdf:value: used only docking predictions, [24], [25], [26]while others suggested (as in this thesis) using a more accurate scoring method (e.g. MM/PBSA (Molecular Mechanics/Poisson Boltzmann Surface Area)) to refine the final selected hits. [>>21<<] All of these approaches, similar to the work presented here, were aiming at keeping the balance between significantly reducing the number of target structures and, in the meantime, retaining their capacity to describe the conformational
n3:mentions: n4:12579579

Subject Item: _:vb19902464
rdf:type: n3:Context
rdf:value: Based on our previous investigations, [>>15<<], the important residues that mostly contribute to its interaction with ligands are Gly109, Pro111, Asn110, Asp 129, Phe140, Tyr145, and Arg156 (Figure 2).
n3:mentions: n4:19473860

Subject Item: _:vb19902465
rdf:type: n3:Context
rdf:value: This adaptive approach was tested on other targets and led to successful outcomes [>>28<<], [29], [30].
n3:mentions: n4:20056466

Subject Item: _:vb19902466
rdf:type: n3:Context
rdf:value: This adaptive approach was tested on other targets and led to successful outcomes [28], [>>29<<], [30]. For MD simulations, starting from the optimal binding mode is the most efficient route to reach equilibrium. Therefore, by running the clustering protocol on each ligand and filtering the hits in terms of the population of the
n3:mentions: n4:20659685

Subject Item: _:vb19902467
rdf:type: n3:Context
rdf:value: The average RMSD for the two compounds was around 6 Å, which is consistent with values obtained in similar studies [>>31<<]. The RMSD for NERI01 (Figure 3-A) was more fluctuating than that of the other compound (Figure 3-B), indicating higher flexibility. This was evident in the atomic fluctuatation analysis. Many parts of NERI01 are flexible (Figure 3-C)
n3:mentions: n4:11543671

Subject Item: _:vb19902468
rdf:type: n3:Context
rdf:value: In this context, our VS protocol utilized the MM-PBSA [>>32<<] to suggest the final ranked set of top hits (see Materials and Methods).
n3:mentions: n4:11123888

Subject Item: _:vb19902469
rdf:type: n3:Context
rdf:value: It was also validated as a VS refining tool and revealed excellent results in predicting the actual binding affinities and in discriminating true binders from inactive (decoy) compounds [>>33<<], [34], [35].
n3:mentions: n4:8451640

Subject Item: _:vb19902470
rdf:type: n3:Context
rdf:value: It was also validated as a VS refining tool and revealed excellent results in predicting the actual binding affinities and in discriminating true binders from inactive (decoy) compounds [33], [>>34<<], [35]. Its main advantages are the lack of adjustable parameters and the option of using a single MD simulation for the complete system to determine all energy values.
n3:mentions: n4:11790605

Subject Item: _:vb19902471
rdf:type: n3:Context
rdf:value: It was also validated as a VS refining tool and revealed excellent results in predicting the actual binding affinities and in discriminating true binders from inactive (decoy) compounds [33], [34], [>>35<<]. Its main advantages are the lack of adjustable parameters and the option of using a single MD simulation for the complete system to determine all energy values.
n3:mentions: n4:11470599

Subject Item: _:vb19902472
rdf:type: n3:Context
rdf:value: Ms−1) through the following equation: KA = KQ τ0 [37], where KA is the association constant, KQ is the biomolecular rate quenching rate constant and τ0 is the average lifetime of the biomolecule without a quencher (τ0 = 10−8 s) [>>38<<]. The results obtained from this study show that the estimated values for KA are greater than the maximum scatter quenching constant of various quenchers with the biopolymers (KQ = 2×1010 Ms−1) [39] which indicates that the observed static
n3:mentions: n4:4795686

Subject Item: _:vb19902473
rdf:type: n3:Context
rdf:value: As aforementioned, NER is a major DNA repair pathway that eliminates DNA lesions induced by UV light [>>40<<]. A deficiency in NER leads to dramatic diseases characterized by hypersensitivity to UV and a prominent clinical and genetic heterogeneity.
n3:mentions: n4:10517972

Subject Item: _:vb19902474
rdf:type: n3:Context
rdf:value: XP is a direct consequence of lacking one out of several NER proteins such as XPA [>>41<<]–[43]. A major syndrome of XP is the hypersensitivity to UV radiation and, consequently, a high susceptibility to produce skin cancer. As the role of XPA within the NER mechanism is to interact with ERCC1 and recruit the XPF-ERCC1
n3:mentions: n4:7675086

Subject Item: _:vb19902475
rdf:type: n3:Context
rdf:value: XP is a direct consequence of lacking one out of several NER proteins such as XPA [41]–[>>43<<]. A major syndrome of XP is the hypersensitivity to UV radiation and, consequently, a high susceptibility to produce skin cancer. As the role of XPA within the NER mechanism is to interact with ERCC1 and recruit the XPF-ERCC1 endonuclease
n3:mentions: n4:18367095

Subject Item: _:vb511093493
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 7
n3:hasRelevantPaperId: n4:23580445

Subject Item: _:vb511093494
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 4
n3:hasRelevantPaperId: n4:21892204

Subject Item: _:vb511093495
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 4
n3:hasRelevantPaperId: n4:15095299

Subject Item: _:vb511093496
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 4
n3:hasRelevantPaperId: n4:25956741

Subject Item: _:vb511093497
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 4
n3:hasRelevantPaperId: n4:26939044

Subject Item: _:vb511093498
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:9052754

Subject Item: _:vb511093499
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:27247238

Subject Item: _:vb511093500
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:22941649

Subject Item: _:vb511093501
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:14576837

Subject Item: _:vb511093502
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:26318993

Subject Item: _:vb511093503
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:31906898

Subject Item: _:vb511093504
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:16076955

Subject Item: _:vb511093505
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:16957145

Subject Item: _:vb511093506
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:21701511

Subject Item: _:vb511093507
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:23807173

Subject Item: _:vb511093508
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:17948053

Subject Item: _:vb511093509
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 3
n3:hasRelevantPaperId: n4:27650543

Subject Item: _:vb511093510
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:12580598

Subject Item: _:vb511093511
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:7891694

Subject Item: _:vb511093512
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:30208165

Subject Item: _:vb511093513
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:12915808

Subject Item: _:vb511093514
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:9722633

Subject Item: _:vb511093515
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:25268380

Subject Item: _:vb511093516
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:18256616

Subject Item: _:vb511093517
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:19153606

Subject Item: _:vb511093518
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:10810335

Subject Item: _:vb511093519
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:28541665

Subject Item: _:vb511093520
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:31369707

Subject Item: _:vb511093521
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:17183314

Subject Item: _:vb511093522
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:10463593

Subject Item: _:vb511093523
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:12679022

Subject Item: _:vb511093524
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:23178497

Subject Item: _:vb511093525
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:10493501

Subject Item: _:vb511093526
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:19332554

Subject Item: _:vb511093527
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:20418188

Subject Item: _:vb511093528
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:21034966

Subject Item: _:vb511093529
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:15055986

Subject Item: _:vb511093530
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:26321360

Subject Item: _:vb511093531
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:10592235

Subject Item: _:vb511093532
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:20846399

Subject Item: _:vb511093533
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:22562137

Subject Item: _:vb511093534
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:9440758

Subject Item: _:vb511093535
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:17882165

Subject Item: _:vb511093536
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:24474685

Subject Item: _:vb511093537
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:22261329

Subject Item: _:vb511093538
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:18343204

Subject Item: _:vb511093539
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:30386247

Subject Item: _:vb511093540
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:10074455

Subject Item: _:vb511093541
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:19023283

Subject Item: _:vb511093542
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:20662484

Subject Item: _:vb511093543
rdf:type: n3:RelevantBibliographicResource
n3:RelevantScore: 2
n3:hasRelevantPaperId: n4:11008124