Structure-based design represents a pivotal methodology in drug discovery, leveraging the three-dimensional structures of biological targets and ligands to innovate new therapeutic agents. This approach commences with determining the structural configuration of biological targets, either via experimental methods or computational predictions. Utilizing these structural insights, researchers engage in rational design of small molecules tailored to the activity and structure of the target proteins. This meticulous process involves not just the discovery but also the intricate modeling of interactions between the ligand and its corresponding protein target.

The venture of structure-based design aims to decode and influence the mechanisms of action for active compounds. Analyzing the three-dimensional configurations of protein-ligand complexes provides an understanding of how these interactions modulate the function of the target protein. Moreover, structure-based virtual screening has advanced as a prominent computational technique, enabling the assessment of vast libraries of compounds for their binding capabilities. This screening facilitates the identification of lead compounds that exhibit both high selectivity and affinity, including the discovery of allosteric modulators that offer the advantage of targeting protein functions without competing with natural ligands.

To delimit the investigation of structure-based design in drug discovery, this article collection seeks to focus on strategic computational approaches and innovative methods, while also emphasizing the efficacy and safety assessment of potential therapeutics. Specifically, the scope includes:

Exploration of transient pocket targeting and allosteric site identification to enhance the precision in hitting therapeutic targets.
Utilization of advanced ADMET prediction and molecular dynamics simulations to refine the safety profiles and binding efficacy of candidates.
In-depth analysis using MM/PBSA methods to quantify the binding energy of ligands, thus providing insights into their potential as lead compounds.
We welcome contributions that address, but are not limited to, the following themes:

Molecular docking and virtual screening for lead compound identification.
Allosteric and transient pocket identification for hit optimization.
Pharmacokinetic and pharmacodynamic predictions to assess drug behavior.
Molecular dynamics simulation for in-depth study of compound interactions.
Comprehensive binding energy calculations to evaluate compound efficacy.

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Frontiers in Drug Discovery

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