About this Research Topic
An active compound's mechanism of action can also be studied using a structure-based design. It is possible to gain insights into how the ligand binds to the target protein and how the complex modulates its function by analyzing the three-dimensional structure of the protein-ligand complex. Structure-based virtual screening is the advanced computational approach used to screen large libraries of compounds for their ability to bind to a target protein. It can identify potential lead compounds with high binding affinity and selectivity. Structure-based design can be used to identify allosteric binding sites on the target protein, which can be exploited to develop drugs with unique properties. Allosteric modulators can bind to a site on the protein that is distinct from the active site, allowing for the modulation of target activity without interfering with natural ligand binding.
Structure-based design can also be used to identify transient pockets and develop compounds that specifically bind to these sites. Transient pockets are small cavities on the protein surface that only exist for a short period of time. These pockets can be targeted with small molecules that bind to the pocket and modulate target protein function. Further, ADMET prediction, molecular dynamics simulation, and binding free energy calculation-MM/PBSA methods are utilized to assess the safety and binding nature of the lead compound(s). A combination of these techniques can be used to investigate lead compound(s) with improved ADMET properties, high binding affinities, and selectivity for their target proteins.
The main goal of this article collection is to provide insightful information on structure-based design and highlight the tremendous potential of computational approaches in drug discovery. The following themes are welcome, but are not limited to:
o Molecular docking and virtual screening to identify the potential lead compound(s).
o Identification of allosteric binding sites and transient pockets for hit identification.
o ADMET prediction to assess the pharmacokinetics and pharmacodynamics of lead compound(s).
o Molecular dynamics simulation to study the behavior of lead compound(s) over time and investigate their interactions with target proteins.
o Binding energy calculations-MM/PBSA analysis to evaluate the strength of lead compound(s).
Keywords: protein modeling, binding site prediction, molecular docking, virtual screening, ADMET prediction, molecular dynamics simulation, binding energy calculation
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