Figure 1.
Architectural tertiary structure of Leishmania major 18S rRNA front and back view. Shown is the 18S rRNA, colored differently depending with domains (5′major—red, Central—green, 3′major—blue, and 3′minor—yellow).
Figure 1.
Architectural tertiary structure of Leishmania major 18S rRNA front and back view. Shown is the 18S rRNA, colored differently depending with domains (5′major—red, Central—green, 3′major—blue, and 3′minor—yellow).
Figure 2.
Architectural tertiary structure of Trypanosoma brucei 18S rRNA front and back view. Shown is the 18S rRNA, colored differently depending on domains (5′major—red, Central—green, 3′major—blue, and 3′minor—yellow).
Figure 2.
Architectural tertiary structure of Trypanosoma brucei 18S rRNA front and back view. Shown is the 18S rRNA, colored differently depending on domains (5′major—red, Central—green, 3′major—blue, and 3′minor—yellow).
Figure 3.
Architectural tertiary structure of Trypanosoma cruzi 18S rRNA front and back view. Shown is the 18S rRNA, colored differently depending on domains (5′major—red, Central—green, 3′major—blue, and 3′minor—yellow).
Figure 3.
Architectural tertiary structure of Trypanosoma cruzi 18S rRNA front and back view. Shown is the 18S rRNA, colored differently depending on domains (5′major—red, Central—green, 3′major—blue, and 3′minor—yellow).
Figure 4.
T. Brucei bound to Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 4.
T. Brucei bound to Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 5.
T. Cruzi bound to Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 5.
T. Cruzi bound to Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 6.
L. Major bound to Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 6.
L. Major bound to Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 7.
T. Brucei + Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 7.
T. Brucei + Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 8.
T. cruzi + Angiolam (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 8.
T. cruzi + Angiolam (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 9.
L. major + Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 9.
L. major + Angiolam. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 10.
T. brucei + Apicuralen (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 10.
T. brucei + Apicuralen (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 11.
T. cruzi + Apicuralen (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 11.
T. cruzi + Apicuralen (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 12.
L. major + Apicuralen. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 12.
L. major + Apicuralen. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 13.
T. Brucei + Archazolid. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 13.
T. Brucei + Archazolid. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 14.
T. cruzi + Archazolid. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 14.
T. cruzi + Archazolid. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 15.
L. major + Archazolid. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 15.
L. major + Archazolid. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 16.
T. brucei + Cittilin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 16.
T. brucei + Cittilin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 17.
T. cruzi + cittilin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 17.
T. cruzi + cittilin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 18.
L. major + cittilin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 18.
L. major + cittilin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 19.
T. Brucei + Epothilone. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 19.
T. Brucei + Epothilone. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 20.
T. cruzi + Epothilone. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 20.
T. cruzi + Epothilone. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 21.
L. major + Epothilone. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 21.
L. major + Epothilone. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 22.
T. cruzi + leupyrin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 22.
T. cruzi + leupyrin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 23.
T. Brucei + leupyrin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 23.
T. Brucei + leupyrin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 24.
L. major + leupyrin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 24.
L. major + leupyrin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 25.
T. Brucei + Myxothiazol. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 25.
T. Brucei + Myxothiazol. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 26.
T. Cruzi + Myxothiazol. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 26.
T. Cruzi + Myxothiazol. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 27.
L. Major + Myxothiazol. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 27.
L. Major + Myxothiazol. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 28.
T. Brucei + Sorangicin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 28.
T. Brucei + Sorangicin. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 29.
L. major + Sorangicin A. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 29.
L. major + Sorangicin A. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 30.
T. Brucei + Sulfangolid A. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 30.
T. Brucei + Sulfangolid A. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 31.
L. Major + Sulfangolid A. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Figure 31.
L. Major + Sulfangolid A. (A): Best binding pose and nucleotides involved. (B): Schematic binding pocket. (C): shows the Nucleotides component that re involved in binding. (D): Shows the main bonds involved between the compound and the nucleotide component.
Table 1.
The three selected Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major sequences selected for this study. L(3) refers to the cell location, which is the nucleus, RT(4) refers to RNA type R = ribosomal RNA (rRNA), RC refers to the RNA Class 16S, Nucleotide size, Cmp means % Complete, Acc means gene bank accession number, common name and the Phylogenetic Classification, m.
Table 1.
The three selected Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major sequences selected for this study. L(3) refers to the cell location, which is the nucleus, RT(4) refers to RNA type R = ribosomal RNA (rRNA), RC refers to the RNA Class 16S, Nucleotide size, Cmp means % Complete, Acc means gene bank accession number, common name and the Phylogenetic Classification, m.
Row # | Organism (2) | L(3) | RT(4) | RC | Size | Cmp | Acc | Common Name | Phylogeny[M] (1) |
---|
1 | Trypanosoma brucei | N | R | 16S | 2251 | 100 | M12676 | kinetoplasts | cellular organisms …» |
2 | Trypanosoma cruzi | N | R | 16S | 2315 | 100 | AF245382 | kinetoplasts | cellular organisms …» |
3 | Leishmania major | N | R | 16S | 2203 | 100 | AC005806 | kinetoplasts | cellular organisms …» |
Table 2.
18S rRNA Energy Optimization Table obtained from results of RNA 123, which helps minimize the energy from a large positive figure to a more acceptable negative figure that is biologically functional.
Table 2.
18S rRNA Energy Optimization Table obtained from results of RNA 123, which helps minimize the energy from a large positive figure to a more acceptable negative figure that is biologically functional.
Species | Name | 18SrRNA.std.egy | 18SrRNA.opt.egy |
---|
Leishmania major | Total Inter energy | 908487.3182 | −83582.63882 |
Total intra energy (-Gamma en | −17864.6686 | −17828.1188 |
Total Gamma Terms Energy | 1746.8654 | 1743.13568 |
Total Gap Geometry Penalty | 3108.37922 | 2746.02559 |
Total Restraint Energy | 0 | 3550.87301 |
TOTAL STRUCTURE ENERGY | 895477.8943 | −96921.59635 |
Trypanosoma brucei | Total Inter energy | 2021190.532 | −102281.5112 |
Total intra energy (-Gamma en | 71145.86365 | 10625.04139 |
Total Gamma Terms Energy | 2357.05629 | 2277.69707 |
Total Gap Geometry Penalty | 24166.41849 | 9500.81691 |
Total Restraint Energy | 0 | 8078.41829 |
TOTAL STRUCTURE ENERGY | 2118859.871 | −79877.95586 |
Trypanosoma cruzi | Total Inter energy | 7208497.219 | −98209.94034 |
Total intra energy (-Gamma en | 208432.083 | −7806.99519 |
Total Gamma Terms Energy | 2458.82781 | 2440.13835 |
Total Gap Geometry Penalty | 35870.86855 | 12018.7965 |
Total Restraint Energy | 0 | 10017.37844 |
TOTAL STRUCTURE ENERGY | 7455258.998 | −91558.00067 |
Table 3.
Myxobacteria Compounds with activity on all more negative kinetoplastids, ACE −400.
Table 3.
Myxobacteria Compounds with activity on all more negative kinetoplastids, ACE −400.
Compound Name | Compounds with Activity on All More Negative Kinetoplastids, ACE −400 |
---|
T. Brucei | T. Cruzi | L. Major |
---|
Angiolam A | −491.7 | −673.71 | −550.93 |
Apicularen B | −549.58 | −529.41 | −585.93 |
Archazolid A | −516.32 | −470.74 | −413.53 |
Cittilin A | −495.42 | −529.71 | −520.78 |
Epothilone B | −573.04 | −513.65 | −346.85 |
Leupyrin | −598.53 | −648.66 | −393.82 |
Myxothiazol | −595.18 | −573.36 | −449.9 |
Sorangicin A | −466.93 | −466.93 | −456.49 |
Spirangien B | −503.52 | −576.45 | −516.62 |
Sulfangolid A | −613.53 | −613.53 | −643.25 |
Table 4.
Showing docking and binding results of the best pose compounds with activity on all more negative kinetoplastids ACE −400.
Table 4.
Showing docking and binding results of the best pose compounds with activity on all more negative kinetoplastids ACE −400.
Compound Name | Compounds with Activity on All More Negative Kinetoplastids ACE −400 | | | |
---|
T. Brucei | | T. Cruzi | | L. Major | |
---|
Angiolam A | −491.7 | G92,G93,A434,A450,G470,G473,G495,U496,U510 | −673.71 | A55,U56,G92,G93,A434,A450,G473,G495,U496,U510 | −550.93 | U1259,G1261,A1262,C1543,G1544,C1545,A1546,C1547,U1548,A1549,C1550,A1551,G1662 |
Apicularen B | −549.58 | G1253,A1254,C1255,A1257,U1258,G1260,U2230,G2231 | −529.41 | G1109,U1110,A1134,C1135,U1150,G1151,U1152,C1153 | −585.93 | U27,A28,A40,G41,G407,A421,U422,U423,A813 |
Archazolid A | −516.32 | G690,U691,U692,A693,G1281,A1282,C1283,A1284,G1460,A1461,A1470,G1471,G1472,U1473,G1478 | −470.74 | C94,U427,A472,C474,A475,G476,G477,C478,A485 | −413.53 | C164,G165,U445,C448,U449,A450,G465,G466, |
Cittilin A | −495.42 | A43,A47,G48,C94,U95,C492,A493,G494,C496TTTT | −529.71 | U716,G719,G738,U740,G741,A742,C1051,U1052 | −520.78 | A26,U27,A40,C419,G420,A421,U422,U423, |
Epothilone B | −573.04 | A55,U56,A90,U91,G92,A468,G513,U514,C515,A527,U528,A530 | −513.65 | U56,A90,G92,A450,U496,C497,A512 | −346.85 | G42,C50,A471,G472,G473,C474,A481 |
Leupyrin | −598.53 | G1532,C1533,A1534,U1663,U1683,G1686,A1690,U1691,A2092,U2093 | −648.66 | C1804,A1807,U1809,A1810,A1813,U1884,U1887 | −393.82 | A103,C105,G107,A108,A347,C349,U350 |
Myxothiazol | −595.18 | A55,U56,G92,U467,A468,C489,G513,U514,C515,A527,U528,A530 | −573.36 | C49,C50,A434,G435,U449,A450,G470,C471,A472,G473, | −449.9 | C203,A205,G206,C218,U224,C225,U227,G228, |
Sorangicin A | −466.93 | A1240,A1241,G1253,C1255,C1256,A1257,U1258,U1259,U2220 | −466.93 | | −456.49 | C235,C236,A237,A304,U306, |
Spirangien B | −503.52 | C59,U60,A64,G79,G80,A520,A521,C525,G526 | −576.45 | A100,G106,G407,G409,C423,G424,A864,A902 | −516.62 | A1294,C1535,C1536,A1538,A1549,A1642,U1644,U1645,A1689 |
Sulfangolid A | −613.53 | A105,G373,C374,G428,A885,U919,A920,C921,A922 | −613.53 | | −643.25 | A26,U27,G41,G407,G408,U422,U423,A813 |