MolADI: A Web Server for Automatic Analysis of Protein-Small Molecule Dynamic Interactions
The MolADI website provides a simple and clear service for protein-small molecule dynamic visualization. The original intention of the entire website is to enable users to analyze and obtain results more easily. Users only need to upload the data files they want to analyze, and can obtain the results quickly. After testing, the analysis time is about 30s, which is more efficient than manual analysis. The results page also provides a wealth of visual results, including 2D and 3D results. The information of each interaction between protein and small molecule can be clearly viewed, such as the location where the interaction occurs, the distance and angle of the interaction, and the interaction in the entire track changes, etc. At the same time, MolADI's multiple filter functions also allow users to locate different interactions of small molecules more easily to further analyze their specific information in the binding site of the receptor, such as how the distance and angle change in the dynamic trajectory.
Figure shows the homepage of MolADI, where users can upload files. Users should provide a structure file in pdb format and a trajectory file in xtc or gro format from GROMACS. The server will automatically process different file formats in the background and proceed to the next step. After jumping to the analysis interface, the front-end page will display some current analysis progress information in real time. The average time for analyzing one file is about 30s.
Figure shows the overview of the result page. The page is divided into two areas. The left half is the 2D interaction information map, which is displayed in the form of a radar chart. The right half is the 3D interaction information. The function column contains the corresponding residue information, the atom pair in interaction and their distance. The area in the page can be zoomed and moved to adjust the viewing angle. The initial result contains all the interaction information related to small molecule in the data file. In the function column on the right, users can select the interaction information of interest to observe. The functionalities are listed below:
♥ Custom displaying information about the type of interaction of interest
There are in total of nine selection boxes in this functional area, including eight specific interaction types, as well as whether to display all of the interactions. The user can click on the selection box of the corresponding type to decide whether to display the corresponding interaction type. The color corresponding to the interaction type is also marked in this area, so that users can better understand the results.
♥ Custom selecting small molecules
This function is used to select which interaction information of small molecule will be displayed. All interactions are displayed by default. All the small molecules are listed in the list. By selecting the interaction of a specific small molecule of interest to display, the contents of two regions (2D region and 3D region) will correspondingly change to show the information of the selected small molecule.
♥ Whether to display the interaction information only
This function is for users to easily observe the interaction information. By default, the structure diagram will be displayed to the user. However, if there is a lot of interaction information generated and the structure is more complex, the structure information may cover the interaction information. This function can be selected to display only the interaction information to better observe the corresponding interaction information.
♥ Camera type
This function provides a stereoscopic display effect, the user first needs to select the stereop mode, and then wear professional glasses to observe the stereoscopic effect.
This function is used to locate the 3D result to the center of the page to facilitate the observation the result.
The above functional areas can be used freely and flexibly to meet the needs for different observation requirements. Finally, the result download function is provided in the upper right corner of the overview page, and the result is saved as a pdf file for users to download. It mainly includes 2D result information.
3D Result Page
Figure shows the function of the 3D page, which is mainly used to display 3D results, providing a larger area for users to better observe the results. Compared to the overview page, a dynamic result display has been added to this page: by clicking the play button in the functional area, the 3D result will play the trajectory and show the interaction information from each frame in a dynamic and circular sequence. The movie can be paused to locate the frame of interest. More conveniently, by sliding the scroll axis on the right side of the button, the user can directly locate a frame to observe. Similarly, this function can also be used in conjunction with other functions of the functional area. For example, users can choose to only observe the dynamic changes of hydrogen bonds of specific small molecules.
2D Result Page
Figure shows the 2D result page, which mainly reflects the interaction information through 2D graphs. In the left half of the area, all interactions are listed in table form. On the right, the first row is the radar chart on the overview page. Note that the list and the radar chart are in one-to-one correspondence. The corresponding interaction can also be selected and displayed through the small molecule selection function (top left). The second row on the right is the heat map of interaction, which reflects the dynamic interaction information in the 2D form, and shows the interaction variations along the trajectory used (when there are less than 50 frames, only the corresponding frame has its interaction information ). The X axis shows the frame serial number. In this figure, a total of 50 frames are selected from the trajectory file uploaded by the user at an intermediate interval. The Y axis shows the specific interaction information, including the interaction type, residues and/or the small molecules involved and the small molecule id. From the heat map, users can clearly see the dynamic changes of a specific interaction in the entire trajectory. The bottom row reflects the stability of the protein structure in the trajectory. The backbone-backbone RMSD, backbone-backbone RMSF, and backbone-ligand RMSD are shown