A Study on the Effect of the Substituent against PAK4 Inhibition Using In Silico Methods
Abstract
:1. Introduction
2. Results
2.1. Molecular Docking Studies against PAK4
2.2. Pair-Interaction Energy Analysis
2.3. Molecular Electrostatic Potential Surface
3. Discussion
4. Materials and Methods
4.1. Molecular Docking Study
4.2. FMO Calculations
4.3. Quantum Mechanics Chemical Calculations
4.4. In Vitro Assay
4.5. Procurement and Synthesis
Author Contributions
Funding
Conflicts of Interest
References
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1 | 2 | 3 | 4 | |
---|---|---|---|---|
Docking score | 59.27 | 56.95 | 54.00 | 58.14 |
Binding energy | −23.78 | −27.14 | −25.16 | −22.78 |
PIE | −22.33 | −22.10 | −21.39 | −16.30 |
IC50 (nM) | 5150 | 8533 | >30,000 | >30,000 |
Residue | I372 | G328 | V335 | I337 | A348 | K350 | V379 | M395 | E396 | F397 | L398 | E399 | G400 | G401 | A402 | L403 | D405 | L447 | S457 | D458 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Compound | |||||||||||||||||||||
1 | −0.45 | −1.37 | −0.75 | 1.35 | −2.99 | −9.84 | −1.66 | −2.33 | 4.84 | −0.25 | −2.88 | −3.48 | −3.88 | 5.08 | −2.55 | −0.71 | −1.70 | −0.99 | −1.67 | 3.88 | |
2 | −0.45 | −1.35 | −0.74 | 1.29 | −3.35 | −9.22 | −1.76 | −2.06 | 4.68 | −0.24 | −3.00 | −3.15 | −3.83 | 4.92 | −2.46 | −0.68 | −1.69 | −1.02 | −1.69 | 3.70 | |
3 | −0.32 | −1.37 | −0.62 | 1.32 | −2.87 | −8.98 | −1.68 | −1.54 | 4.38 | −0.16 | −2.72 | −3.85 | −3.92 | 5.14 | −2.52 | −0.75 | −1.99 | −0.83 | −1.40 | 3.29 | |
4 | −1.20 | −1.21 | −1.28 | 0.89 | −3.86 | −6.28 | −1.78 | −1.20 | 5.09 | −0.62 | −6.57 | 2.74 | −3.29 | 3.65 | −2.64 | −0.47 | −0.82 | −1.94 | −2.21 | 4.19 |
Residue | I372 | G328 | V335 | I337 | A348 | K350 | V379 | M395 | E396 | F397 | L398 | E399 | G400 | G401 | A402 | L403 | D405 | L447 | S457 | D458 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Compound | |||||||||||||||||||||
1 | −0.24 | −2.30 | −0.97 | 1.64 | −3.47 | −12.30 | −1.58 | −1.24 | 5.18 | −0.01 | −4.37 | −8.26 | −5.37 | 3.87 | −2.54 | −1.67 | −5.82 | −1.37 | −1.62 | 6.89 | |
2 | −0.24 | −2.26 | −0.97 | 1.58 | −3.43 | −11.53 | −1.56 | −1.23 | 5.09 | −0.01 | −4.44 | −7.92 | −5.29 | 3.71 | −2.45 | −1.62 | −5.69 | −1.39 | −1.65 | 6.73 | |
3 | −0.17 | −2.33 | −0.90 | 1.69 | −3.48 | −12.83 | −1.62 | −1.30 | 5.27 | 0.22 | −4.24 | −8.30 | −5.40 | 3.90 | −2.49 | −1.71 | −5.90 | −1.28 | −1.61 | 6.95 | |
4 | −0.86 | −1.99 | −1.50 | 1.11 | −4.02 | −6.48 | −1.58 | −1.06 | 4.75 | −0.60 | −7.28 | −3.85 | −4.86 | 2.71 | −2.71 | −1.40 | −4.77 | −2.27 | −2.35 | 5.82 |
Residue | I372 | G328 | V335 | I337 | A348 | K350 | V379 | M395 | E396 | F397 | L398 | E399 | G400 | G401 | A402 | L403 | D405 | L447 | S457 | D458 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Compound | |||||||||||||||||||||
1 | 0.00 | −0.01 | 0.00 | 0.00 | 0.03 | 0.06 | −0.01 | −0.05 | 0.00 | −0.06 | 0.02 | −2.28 | −0.16 | 0.05 | −0.03 | 0.00 | 0.00 | 0.01 | −0.03 | 0.00 | |
2 | 0.00 | −0.01 | 0.00 | 0.00 | 0.09 | 0.13 | −0.03 | −0.03 | 0.00 | −0.06 | −0.01 | −2.18 | −0.16 | 0.05 | −0.03 | 0.00 | 0.00 | 0.01 | −0.03 | 0.00 | |
3 | 0.00 | −0.01 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | −0.06 | −0.01 | −2.15 | −0.16 | 0.05 | −0.03 | 0.00 | 0.00 | 0.01 | 0.00 | 0.00 | |
4 | −0.01 | −0.01 | −0.01 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | −0.02 | −0.39 | −0.95 | −0.10 | −0.05 | −0.02 | 0.00 | 0.00 | −0.01 | 0.01 | 0.00 |
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Yoon, H.R.; Chai, C.C.; Kim, C.H.; Kang, N.S. A Study on the Effect of the Substituent against PAK4 Inhibition Using In Silico Methods. Int. J. Mol. Sci. 2022, 23, 3337. https://doi.org/10.3390/ijms23063337
Yoon HR, Chai CC, Kim CH, Kang NS. A Study on the Effect of the Substituent against PAK4 Inhibition Using In Silico Methods. International Journal of Molecular Sciences. 2022; 23(6):3337. https://doi.org/10.3390/ijms23063337
Chicago/Turabian StyleYoon, Hye Ree, Chong Chul Chai, Cheol Hee Kim, and Nam Sook Kang. 2022. "A Study on the Effect of the Substituent against PAK4 Inhibition Using In Silico Methods" International Journal of Molecular Sciences 23, no. 6: 3337. https://doi.org/10.3390/ijms23063337