Molecular dynamics simulation of the interaction between the Tenebrio molitor alpha-amylase and its inhibitor at different proportion of crystal water was carried out with OPLS force field by hyperchem 7.5 software. In the correlative study, the optimal temperature of wheat monomeric and dimeric protein inhibitors was from 273 K to 318 K. The the average temperature of experimentation is 289 K. (1) The optimal temperature of interaction between alpha-amylase and its inhibitors was 280 K without crystal water that was close to the results of experimentation. The forming of enzyme-water and inhibitor-water was easy, but incorporating third monomer was impossible. (2) Having analyzed the potential energy data, the optimal temperature of interaction energy between alpha-amylase and its inhibitors covering 9 : 1, 5 : 5, 4 : 6, and 1 : 9 proportion crystal water was 290 K. (3) We compared the correlative QSAR properties. The proportion of crystal water was close to the data of polarizability (12.4%) in the QSAR properties. The optimal temperature was 280 K. This result was close to 289 K. These findings have theoretical and practical implications.
Alpha-amylases (1, 4-
Enzyme inhibitors are important tools of nature for regulating the
activity of enzymes in cases of emergency. Plant seeds are known to produce a
variety of enzyme inhibitors that are thought to protect the seed against
insects and microbial pathogens. Proteinase inhibitors are the best studied of
this group [
The major alpha-amylases inhibitor (AAI) present in the seeds of
Amaranthus hypochondriacus,
a variety of the Mexican crop plant amaranth, is a 32-residue-long polypeptide
containing 6 cysteines, with 1–4, 2–5, 3–6 three disulfide
bridges. It is the shortest alpha-amylases inhibitor described so far which has
no known close homologs in the sequence data bases [
Quantitative structure-activity
relationship (QSAR) represents an attempt to relate structural descriptors of
molecules with their physicochemical properties and biological activities. It
is widely used for the prediction of physicochemical properties in chemical, environmental,
and pharmaceutical areas [
In this work, we selected the structure of alpha-amylases from Tenebrio molitor larvae (containing 471 amino acid residues) and inhibitor from the amaranth. A number of crystal waters were distributed to alpha-amylases and their inhibitors manually using hyperchem 7.5 software according to different proportion via molecular dynamics simulation. The Tenebrio molitor alpha-amylase and the amaranth alpha-amylase inhibitor QSAR properties were calculated. The results showed that the crystal water had affected in the interaction between the alpha-amylases and their inhibitors. These findings have theoretical and practical implications.
The structure of Tenebrio molitor alpha-amylase, the amaranth
alpha-amylase inhibitor, and crystal water (containing 273 molecules) was taken
from 1clv (
All modeling procedures, including energy minimization and molecular
dynamics, were performed using the hyperchem 7.5 software. Energy calculations
were carried out using the OPLS force field. Optimized molecular structure
until the maximum energy derivative was lower than 0.1 kcal/moL (0.418 kJ/moL)
in order to obtain a correct geometry. Dynamics simulation was performed using
a time step of 0.5femtosecond, and the temperature was altering 10 K from 270 K
to 370 K. There were 3 processes in simulation. Firstly, heating, from 0 K to simulation temperature using 7 K
per step, heating time was 0.1 ps. Secondly, simulating, simulation time was 20
picoseconds in simulation temperature. Finally, annealing, from simulation
temperature to 0 K using 7 K per step, annealing time was
0.1 picosecond [
Recent research showed that enzymes had been used on all conformation not only during catalysis but also
before catalysis. Since the protein motions necessary for catalysis were an
intrinsic property of the enzyme, motion was localized not only to the active
site but also to a wider dynamic network [
The energy of
interaction was calculated from experimental data using the following equation [
Since predictions from any QSAR models cannot be intrinsically better than the experimental data employed to develop the model, the quality of the input data will greatly influence the QSAR model performance. In order to build a QSAR model with good generalized performance, a preliminary analysis for the quality of the data set (mainly the detection of outliers) was performed by modeling the complete set of alpha-amylase and its inhibitor.
The QSAR properties of alpha-amylase and its inhibitor were provided in
Table
The QSAR properties of inhibitor and alpha-amylase.
Species | |||
---|---|---|---|
QSAR | Inhibitor | alpha-amylase | Inhibitor/alpha-amylase (%) |
Partial charges | 0.00 | 0.00 | — |
Surface area[approx.] | 5220.84 | over | — |
Surface area[grid] | 8104.71 | 50393.60 | 16.1 |
Volume | 6860.60 | 43349.11 | 15.8 |
Hydration energy | 2214.75 | over | — |
Log P | 0.1 | ||
Refractivity | 871.39 | 6694.71 | 13.0 |
Polarizability | 351.61 | 2826.71 | 12.4 |
Mass | 3661.59 | 51193.14 | 7.2 |
Because the inhibitor and alpha-amylase were neutral molecules, so their partial
charges were zero in Table
We calculated the interaction energy among 3 monomers according to (
The respective chart of
This information showed that the interaction energy between crystal water and alpha-amylase inhibitor was negative from 270 K to 370 K, which showed that they were combined and reacted among crystal water, alpha-amylase, and its inhibitor. As temperature increases, the interaction energy between alpha-amylase and its inhibitor tends to get smaller. However, the interaction energy between crystal water and alpha-amylase inhibitor was negative, and the numerical value was very big from 270 K to 370 K.The results showed that it was easy to combine between crystal water and alpha-amylase inhibitor.
Analysis of the results indicated that the interaction energy between alpha-amylase and its inhibitor was negative from 270 K to 370 K. The forming of inhibitor-water was easy, but the incorporating alpha-amylase was impossible.
The interaction energy between alpha-amylase and its inhibitor was negative, and the numerical value was very big from 270 K to 370 K. The forming of enzyme-water was easy, but the incorporating inhibitor was impossible.
The result was as follows: the forming of enzyme-water and inhibitor-water was easy, but the incorporating third monomer was impossible.
The interaction energy between alpha-amylase and inhibitor covering
different proportion of crystal water was calculated according to (
The compositive chart of Δ
The respective chart of
From Figure
From Figure
The absolute value of the interaction energy was the greatest at 300 K when the distributed proportion of crystal water was 9 : 1, 8 : 2, 7 : 3, 5 : 5, 4 : 6, 3 : 7, and 1 : 9. The results showed the optimal temperature via molecular dynamics simulation which was agreed with the results of experimentation. And the binding of alpha-amylase average temperature was 289 K.The interaction energy between alpha-amylase and its inhibitor was on the nadir at 290 K in figure when the distributed proportion of crystal water was 9 : 1, 5 : 5, 4 : 6, and 1 : 9. In the case of 1 : 9, the optimal temperature may be related to some QSAR properties.
The interaction energy between alpha-amylase and its inhibitor was on the nadir at 340 K, 330 K when the distributed proportion of crystal water was, respectively, 6 : 4 and 2 : 8. These results were disagreeing with the experimental results that may be caused by the distributed proportion of crystal water and others causation, which had studied as follow.
For the sake of an accurate result, we must treat jointly the experimental results related to some QSAR properties. In the case of 1 : 9 (about 11.1%), the interaction energy between alpha-amylase and its inhibitor was the greatest in all figures above, and this proportion of crystal water was close to the data of polarizability (12.4%) in the QSAR properties. This indicated that polarizability of the QSAR properties possibly had higher influence to the interaction. We want to validate below that polarizability affected reactive temperature condition of interaction between alpha-amylase and its inhibitor.
We calculated the interaction energy between alpha-amylase and its
inhibitor covering (87.6 : 12.4) proportion of crystal water according to (
The chart of Δ