A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit <a rel="external noopener" href="http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3820560&blobtype=pdf">the original URL</a>. The file type is <code>application/pdf</code>.
<i title="Bentham Science Publishers Ltd.">
<a target="_blank" rel="noopener" href="https://fatcat.wiki/container/zicjy4mtnrfahfmtoo4ufy5g6u" style="color: black;">Current drug metabolism</a>
As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting protein-ligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues,<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.2174/138920012799362837">doi:10.2174/138920012799362837</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/arxeeeslsvbdvgkjmzenhxp7pe">fatcat:arxeeeslsvbdvgkjmzenhxp7pe</a> </span>
more »... may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches. Keywords Structure-based drug design; protein modeling; focused library design; pharmacophore; flexible docking; high-throughput virtual screening; de novo design; protein-protein interaction; polypharmacology Modern computational-aided drug design established a novel platform by which researchers perform in-depth in silico simulation prior to labor-extensive wet-lab validation  . It comprises of two major parts corresponding to the information of molecular source it utilizes: structure-based (or receptor-based) drug design and ligand-based drug design. Structure-based drug design, which relies on the knowledge of biological target structures, aims to discover small molecules/peptides leads with desired chemistry properties, and orchestrate the following experimental validation and lead optimization. Structure-based approach provides mechanism-based basis, where potential ligands are excavated using receptor-dependent parameters, while ligand-based approaches bypass the consideration of complex biomolecular "black box" in a living cell. This in silico method permeates all aspects of drug discovery today , and we expect it will draw more attentions with the unprecedented advances of computational power and modeling accuracy in this decade.
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200209101939/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3820560&blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/69/44/69448e763e75b546fe192a300ff0729562da23e3.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.2174/138920012799362837"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a>