Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies
Abstract
:1. Introduction
2. Results and Discussion
2.1. Results of the QSAR Models
2.2. Molecular Docking Results
3. Materials and Methods
3.1. Dataset Collection and Pre-Processing
3.2. QSAR Methodology
3.3. Molecular Docking
3.4. IFP Calculations
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
3D | three-dimensional |
AA | amino acid |
HB | Hydrogen bonding |
IFPs | interaction fingerprints analysis |
LasB | Pseudomona elastase |
NAMdP | N-alpha-mercaptoacetyl dipeptide |
PDB | Protein Data Bank |
RMSD | root mean square deviation |
SAR | structure–activity relationship |
References
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NAMdP | Experimental pKi | Predicted pKi | QSAR Set | Glide Score (kcal/mol) | RMSD (Å) | %RefMatch | %MolMatch | |
---|---|---|---|---|---|---|---|---|
1 | HSCH2CO–Ala–Arg–NH2 | −2.0607 | −2.3215 | Training | −7.652 | 0.95 | 38 | 67 |
2 | HSCH2CO–Ala–Asp–NH2 | −2.4997 | −2.1689 | Training | −5.239 | 0.95 | 38 | 78 |
3 | HSCH2CO–Ala–Leu–NH2 | −1.3222 | −2.1287 | Training | −5.067 | 0.96 | 38 | 78 |
4 | HSCH2CO–Ala–Lys–NH2 | −2.1847 | −2.3482 | Training | −5.975 | 0.94 | 38 | 74 |
5 | HSCH2CO–Ala–Trp–NH2 | −2.5966 | −2.3854 | Training | −5.161 | 3.09 | 62 | 96 |
6 | HSCH2CO–Ala–Val–NH2 | −1.7076 | −2.1121 | Test | −4.774 | 0.95 | 38 | 82 |
7 | HSCH2CO–Arg–Asp–NH2 | −2.8129 | −2.3112 | Test | −5.663 | 0.94 | 43 | 67 |
8 | HSCH2CO–Arg–Lys–NH2 | −2.1303 | −2.4909 | Training | −7.267 | 0.91 | 43 | 64 |
9 | HSCH2CO–Arg–Phe–NH2 | −2.3502 | −2.2621 | Training | −6.318 | 1.05 | 46 | 63 |
10 | HSCH2CO–Arg–Trp–NH2 | −2.0969 | −2.5236 | Training | −6.212 | 3.01 | 68 | 83 |
11 | HSCH2CO–Asn–Arg–NH2 | −2.4472 | −2.4689 | Training | −8.582 | 0.98 | 46 | 71 |
12 | HSCH2CO–Asn–Leu–NH2 | −2.7059 | −2.2637 | Training | −5.526 | 0.97 | 46 | 81 |
13 | HSCH2CO–Asn–Lys–NH2 | −2.4609 | −2.4835 | Test | −6.439 | 0.97 | 46 | 77 |
14 | HSCH2CO–Asn–Phe–NH2 | −1.5682 | −2.2525 | Training | −6.015 | 1.00 | 49 | 75 |
15 | HSCH2CO–Asn–Trp–NH2 | −1.8451 | −2.5190 | Training | −5.518 | 2.87 | 70 | 96 |
16 | HSCH2CO–Asn–Val–NH2 | −2.2553 | −2.2475 | Training | −5.682 | 0.99 | 46 | 85 |
17 | HSCH2CO–Asp–Arg–NH2 | −2.7412 | −2.5774 | Training | −8.351 | 0.98 | 46 | 71 |
18 | HSCH2CO–Asp–Leu–NH2 | −2.0719 | −2.3721 | Test | −5.413 | 0.95 | 46 | 81 |
19 | HSCH2CO–Asp–Lys–NH2 | −2.6911 | −2.5914 | Training | −5.397 | 0.96 | 46 | 77 |
20 | HSCH2CO–Asp–Trp–NH2 | −2.3160 | −2.6275 | Training | −4.564 | 2.86 | 70 | 96 |
21 | HSCH2CO–Cys–Arg–NH2 | −2.8102 | −2.4454 | Training | −5.857 | 1.18 | 41 | 68 |
22 | HSCH2CO–Cys–Lys–NH2 | −2.4378 | −2.4601 | Training | −3.691 | 1.18 | 41 | 75 |
23 | HSCH2CO–Cys–Phe–NH2 | −2.1173 | −2.2302 | Test | −3.155 | 0.97 | 43 | 73 |
24 | HSCH2CO–Cys–Trp–NH2 | −2.0334 | −2.4966 | Test | −3.091 | 3.05 | 65 | 96 |
25 | HSCH2CO–Cys–Val–NH2 | −2.2068 | −2.2235 | Training | −2.802 | 0.95 | 41 | 83 |
26 | HSCH2CO–Gln–Arg–NH2 | −2.3365 | −2.4675 | Test | −8.794 | 0.97 | 43 | 64 |
27 | HSCH2CO–Gln–Leu–NH2 | −2.7324 | −2.2627 | Test | −6.350 | 0.95 | 43 | 73 |
28 | HSCH2CO–Gln–Lys–NH2 | −2.5798 | −2.4815 | Test | −6.717 | 0.94 | 43 | 70 |
29 | HSCH2CO–Gln–Trp–NH2 | −1.9590 | −2.5192 | Training | −6.093 | 2.93 | 68 | 89 |
30 | HSCH2CO–Gln–Val–NH2 | −2.9717 | −2.2451 | Training | −6.254 | 0.93 | 43 | 76 |
31 | HSCH2CO–Glu–Lys–NH2 | −2.7427 | −2.6041 | Training | −5.895 | 0.93 | 43 | 70 |
32 | HSCH2CO–Glu–Phe–NH2 | −2.1644 | −2.3753 | Training | −4.813 | 1.15 | 46 | 68 |
33 | HSCH2CO–Glu–Trp–NH2 | −2.8476 | −2.6418 | Training | −5.828 | 2.97 | 68 | 89 |
34 | HSCH2CO–Glu–Val–NH2 | −2.8633 | −2.3677 | Training | −6.019 | 0.96 | 43 | 76 |
35 | HSCH2CO–Gly–Arg–NH2 | −2.8069 | −2.5394 | Training | −8.393 | 0.94 | 35 | 65 |
36 | HSCH2CO–Gly–Leu–NH2 | −2.1399 | −2.3336 | Training | −5.225 | 0.94 | 35 | 76 |
37 | HSCH2CO–Gly–Lys–NH2 | −2.6542 | −2.5543 | Training | −6.274 | 0.94 | 35 | 72 |
38 | HSCH2CO–Gly–Phe–NH2 | −1.7076 | −2.3247 | Training | −5.604 | 0.97 | 38 | 70 |
39 | HSCH2CO–Gly–Trp–NH2 | −2.0864 | −2.5911 | Training | −5.584 | 3.16 | 59 | 96 |
40 | HSCH2CO–Gly–Val–NH2 | −2.6599 | −2.3163 | Training | −5.022 | 0.94 | 35 | 81 |
41 | HSCH2CO–His–Ala–NH2 | −0.5587 | −1.6658 | Training | −3.155 | 0.93 | 38 | 70 |
42 | HSCH2CO–His–Leu–NH2 | −2.4857 | −1.68 | Training | −3.252 | 0.92 | 38 | 61 |
43 | HSCH2CO–His–Lys–NH2 | −2.5211 | −1.8976 | Training | −3.563 | 0.96 | 38 | 58 |
44 | HSCH2CO–His–Phe–NH2 | −1.3222 | −1.6688 | Training | −3.128 | 0.95 | 41 | 58 |
45 | HSCH2CO–His–Trp–NH2 | −1.2553 | −1.9353 | Training | −3.052 | 3.10 | 62 | 79 |
46 | HSCH2CO–His–Val–NH2 | −1.6721 | −1.6632 | Training | −2.932 | 0.94 | 38 | 64 |
47 | HSCH2CO–Ile–Asp–NH2 | −2.1523 | −1.5871 | Training | −4.167 | 1.00 | 43 | 76 |
48 | HSCH2CO–Ile–Gln–NH2 | −0.5717 | −0.5951 | Training | −6.036 | 0.92 | 43 | 73 |
49 | HSCH2CO–Ile–Leu–NH2 | −0.1004 | −1.5472 | Training | −4.684 | 0.94 | 43 | 76 |
50 | HSCH2CO–Ile–Lys–NH2 | −2.2788 | −1.7662 | Training | −5.633 | 0.95 | 43 | 73 |
51 | HSCH2CO–Ile–Thr–NH2 | −0.5328 | −1.3756 | Test | −6.040 | 0.93 | 43 | 80 |
52 | HSCH2CO–Ile–Trp–NH2 | −2.5635 | −1.8041 | Training | −5.822 | 2.92 | 68 | 93 |
53 | HSCH2CO–Ile–Tyr–NH2 | −0.3139 | 0.226 | Training | −5.897 | 0.94 | 46 | 68 |
54 | HSCH2CO–Ile–Val–NH2 | −0.2625 | −1.5298 | Training | −4.851 | 0.93 | 43 | 80 |
55 | HSCH2CO–Leu–Arg–NH2 | −2.7945 | −2.013 | Test | −7.750 | 1.16 | 46 | 71 |
56 | HSCH2CO–Leu–Asp–NH2 | −2.7686 | −1.8479 | Training | −4.075 | 1.10 | 46 | 81 |
57 | HSCH2CO–Leu–Leu–NH2 | −1.7243 | −1.8061 | Training | −5.417 | 1.23 | 46 | 81 |
58 | HSCH2CO–Leu–Lys–NH2 | −1.1461 | −2.0253 | Test | −5.291 | 1.10 | 46 | 77 |
59 | HSCH2CO–Leu–Phe–NH2 | −2.0531 | −1.7966 | Training | −3.977 | 1.26 | 49 | 75 |
60 | HSCH2CO–Leu–Trp–NH2 | −2.4771 | −2.0634 | Training | −4.790 | 2.98 | 70 | 96 |
61 | HSCH2CO–Lys–Asp–NH2 | −2.9872 | −2.4763 | Test | −6.095 | 0.97 | 43 | 73 |
62 | HSCH2CO–Lys–Leu–NH2 | −2.0899 | −2.4284 | Training | −6.349 | 0.96 | 43 | 73 |
63 | HSCH2CO–Lys–Lys–NH2 | −2.6365 | −2.6554 | Training | −7.149 | 0.96 | 43 | 70 |
64 | HSCH2CO–Lys–Phe–NH2 | −2.1004 | −2.4267 | Training | −6.502 | 0.97 | 46 | 68 |
65 | HSCH2CO–Lys–Val–NH2 | −2.7443 | −2.4166 | Training | −6.072 | 0.96 | 43 | 76 |
66 | HSCH2CO–Met–Arg–NH2 | −0.8195 | −1.8487 | Training | −7.798 | 1.00 | 43 | 67 |
67 | HSCH2CO–Met–Asp–NH2 | −0.8451 | −1.6836 | Training | −4.891 | 0.99 | 43 | 76 |
68 | HSCH2CO–Met–Lys–NH2 | −0.5866 | −1.8627 | Training | −6.684 | 0.97 | 43 | 73 |
69 | HSCH2CO–Met–Phe–NH2 | −2.9380 | −1.6339 | Training | −5.564 | 1.19 | 46 | 71 |
70 | HSCH2CO–Met–Trp–NH2 | −2.3096 | −1.9004 | Training | −4.916 | 2.89 | 68 | 93 |
71 | HSCH2CO–Met–Tyr–NH2 | −0.5623 | 0.1316 | Training | −5.955 | 1.26 | 46 | 68 |
72 | HSCH2CO–Met–Val–NH2 | −1.9912 | −1.6213 | Training | −5.815 | 0.97 | 43 | 80 |
73 | HSCH2CO–Phe–Gln–NH2 | 0.1226 | −0.2028 | Training | −6.245 | 0.96 | 38 | 56 |
74 | HSCH2CO–Phe–Ile–NH2 | −0.6503 | −1.1362 | Training | −5.120 | 0.93 | 38 | 58 |
75 | HSCH2CO–Phe–Leu–NH2 | −2.8096 | −1.146 | Training | −4.450 | 0.95 | 38 | 58 |
76 | HSCH2CO–Phe–Lys–NH2 | −1.8808 | −1.3642 | Test | −5.413 | 0.95 | 38 | 56 |
77 | HSCH2CO–Phe–Met–NH2 | −0.4502 | −0.7559 | Training | −6.914 | 0.91 | 38 | 58 |
78 | HSCH2CO–Phe–Phe–NH2 | −2.1644 | −1.1354 | Training | −5.606 | 1.23 | 41 | 56 |
79 | HSCH2CO–Phe–Trp–NH2 | −2.3139 | −1.4029 | Training | −7.568 | 1.76 | 62 | 77 |
80 | HSCH2CO–Phe–Tyr–NH2 | 1.3872 | 0.6276 | Training | −6.918 | 0.95 | 41 | 54 |
81 | HSCH2CO–Phe–Val–NH2 | −1.0414 | −1.1315 | Training | −4.537 | 0.96 | 38 | 61 |
82 | HSCH2CO–Pro–Arg–NH2 | −1.7482 | −2.2055 | Training | −7.338 | 1.53 | 38 | 73 |
83 | HSCH2CO–Pro–Leu–NH2 | −2.3909 | −2.0021 | Training | −7.612 | 1.40 | 38 | 85 |
84 | HSCH2CO–Pro–Lys–NH2 | −2.8842 | −2.2260 | Training | −8.277 | 1.75 | 38 | 81 |
85 | HSCH2CO–Pro–Trp–NH2 | −2.7497 | −2.2623 | Training | −5.630 | 2.96 | 62 | 96 |
86 | HSCH2CO–Pro–Val–NH2 | −2.1959 | −1.9837 | Test | −7.628 | 1.48 | 38 | 92 |
87 | HSCH2CO–Ser–Arg–NH2 | −2.6474 | −2.4949 | Test | −8.952 | 0.94 | 41 | 68 |
88 | HSCH2CO–Ser–Leu–NH2 | −2.7076 | −2.2896 | Training | −6.262 | 1.14 | 41 | 79 |
89 | HSCH2CO–Ser–Phe–NH2 | −1.8751 | −2.2801 | Training | −6.316 | 1.15 | 43 | 73 |
90 | HSCH2CO–Ser–Val–NH2 | −2.3598 | −2.2737 | Training | −5.362 | 1.12 | 41 | 83 |
91 | HSCH2CO–Thr–Arg–NH2 | −2.7896 | −2.2227 | Training | −9.096 | 1.07 | 41 | 65 |
92 | HSCH2CO–Thr–Phe–NH2 | −2.3522 | −2.0078 | Test | −5.473 | 1.13 | 43 | 70 |
93 | HSCH2CO–Thr–Trp–NH2 | −1.8129 | −2.2743 | Training | −6.166 | 2.99 | 65 | 92 |
94 | HSCH2CO–Thr–Val–NH2 | −2.5763 | −2.0035 | Training | −5.808 | 1.06 | 41 | 79 |
95 | HSCH2CO–Trp–Arg–NH2 | −1.3979 | −1.1114 | Test | −8.417 | 0.94 | 38 | 47 |
96 | HSCH2CO–Trp–Asp–NH2 | −1.5798 | −0.9463 | Training | −6.044 | 0.96 | 38 | 52 |
97 | HSCH2CO–Trp–Glu–NH2 | −1.9590 | −0.9930 | Training | −6.483 | 0.99 | 38 | 50 |
98 | HSCH2CO–Trp–Ile–NH2 | −0.0128 | −0.8916 | Training | −7.636 | 0.51 | 38 | 52 |
99 | HSCH2CO–Trp–Leu–NH2 | −0.5635 | −0.9039 | Training | −5.190 | 0.95 | 38 | 52 |
100 | HSCH2CO–Trp–Lys–NH2 | −1.0000 | −1.1254 | Training | −8.613 | 0.66 | 38 | 50 |
101 | HSCH2CO–Trp–Phe–NH2 | −0.0414 | −0.8966 | Test | −6.127 | 1.04 | 41 | 50 |
102 | HSCH2CO–Trp–Trp–NH2 | −1.6902 | −1.1641 | Training | −5.961 | 3.04 | 62 | 70 |
103 | HSCH2CO–Trp–Tyr–NH2 | 1.3925 | 0.8661 | Training | −5.518 | 0.98 | 41 | 48 |
104 | HSCH2CO–Trp–Val–NH2 | −0.6096 | −0.8870 | Training | −5.893 | 0.98 | 38 | 54 |
105 | HSCH2CO–Tyr–Arg–NH2 | −0.4698 | −1.0968 | Training | −10.083 | 0.59 | 38 | 50 |
106 | HSCH2CO–Tyr–Asp–NH2 | −0.7404 | −0.9317 | Training | −6.700 | 0.43 | 38 | 56 |
107 | HSCH2CO–Tyr–Glu–NH2 | −1.4314 | −0.9771 | Training | −7.712 | 0.47 | 38 | 54 |
108 | HSCH2CO–Tyr–Leu–NH2 | −1.5185 | −0.8919 | Training | −7.353 | 0.43 | 38 | 56 |
109 | HSCH2CO–Tyr–Lys–NH2 | −0.9294 | −1.1111 | Training | −8.097 | 0.52 | 38 | 54 |
110 | HSCH2CO–Tyr–Phe–NH2 | −0.8129 | −0.8823 | Test | −7.380 | 0.50 | 41 | 54 |
111 | HSCH2CO–Tyr–Trp–NH2 | −1.1461 | −1.1498 | Training | −7.392 | 2.81 | 62 | 74 |
112 | HSCH2CO–Tyr–Tyr–NH2 | −0.3181 | 0.8790 | Test | −7.686 | 0.87 | 41 | 52 |
113 | HSCH2CO–Tyr–Val–NH2 | 0.1146 | −0.8746 | Training | −7.274 | 0.46 | 38 | 58 |
114 | HSCH2CO–Val–Arg–NH2 | −1.8388 | −1.8918 | Training | −8.183 | 1.00 | 41 | 65 |
115 | HSCH2CO–Val–Leu–NH2 | −1.8388 | −1.6874 | Test | −5.767 | 0.94 | 41 | 75 |
116 | HSCH2CO–Val–Lys–NH2 | −1.3424 | −1.9057 | Training | −5.501 | 0.95 | 41 | 71 |
117 | HSCH2CO–Val–Phe–NH2 | −1.8573 | −1.6755 | Training | −5.001 | 0.95 | 43 | 70 |
118 | HSCH2CO–Val–Val–NH2 | −1.0000 | −1.6676 | Test | −5.225 | 0.95 | 41 | 79 |
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Velázquez-Libera, J.L.; Murillo-López, J.A.; F. de la Torre, A.; Caballero, J. Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies. Int. J. Mol. Sci. 2019, 20, 6133. https://doi.org/10.3390/ijms20246133
Velázquez-Libera JL, Murillo-López JA, F. de la Torre A, Caballero J. Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies. International Journal of Molecular Sciences. 2019; 20(24):6133. https://doi.org/10.3390/ijms20246133
Chicago/Turabian StyleVelázquez-Libera, José Luis, Juliana Andrea Murillo-López, Alexander F. de la Torre, and Julio Caballero. 2019. "Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies" International Journal of Molecular Sciences 20, no. 24: 6133. https://doi.org/10.3390/ijms20246133