Structural determination of midazolam/beta-cyclodextrin inclusion complex by an already proposed protocol and molecular docking studies by quantitative analysis

A lot of interest has been seen in computational methods that provide higher degree of accuracy and reliability, in structural determination and intermolecular interaction of different molecular systems. In the present work, atom accurate structure of beta-cyclodextrin (beta-CD) and midazolam (MDZ) was determined by a combination of NMR (2D-ROESY) and computational methods (MD) using quantitative approach, as developed and proved to be reliable by us previously. Further, we determined the structure of MDZ/beta-CD inclusion complex by using molecular docking studies. Then, the structure obtained by molecular docking studies was compared with the previously developed method by quantitative approach. Parallel results were seen for the structure obtained by our method as well molecular docking approach. This validates the atom accuracy of the structures obtained by both MD and molecular docking. Moreover, both the methods have advantages as well as disadvantages. The advantages of both the methods are that they are less time consuming and cheap. However, main disadvantage of MD is that final structure depends on initial frame and structure obtained from molecular docking depends on dimension of grid box and Cartesian coordinates. Therefore, both methods need to be performed several times to obtain atom accurate and reliable structures.