Hi Sergei I assume that you used the term "drug-like fragments" because you would like to sort out candidates? The paper referenced by Bernhard is a good way to go, but it reflects exactly the problem of PPIs, namely that proteins with well defined binding pockets for substrates (such as kinases) are easily recognized while the algorithm has problems finding pockets of other PPIs.
I get the feeling that a more directed approach is to test the fragments in vitro rather than by simulation. The thought behind is to select for fragments that show measurable effects with fast and material-saving methods rather than focusing on putative pockets that might or not be recognized by your fragments. A good example of such a work-flow is https://pubmed.ncbi.nlm.nih.gov/23344974/ best, matthias [https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image.png]<https://pubmed.ncbi.nlm.nih.gov/23344974/> Using a fragment-based approach to target protein-protein interactions - PubMed<https://pubmed.ncbi.nlm.nih.gov/23344974/> pubmed.ncbi.nlm.nih.gov The ability to identify inhibitors of protein-protein interactions represents a major challenge in modern drug discovery and in the development of tools for chemical biology. In recent years, fragment-based approaches have emerged as a new methodology in drug discovery; however, few examples of smal … Dr. Matthias Barone AG Kuehne, Rational Drug Design Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) Robert-Rössle-Strasse 10 13125 Berlin Germany Phone: +49 (0)30 94793-284 ________________________________ From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Sergei Strelkov <sergei.strel...@kuleuven.be> Sent: Monday, January 25, 2021 8:02:07 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Characterising potential drug-binding pockets Dear everyone, In a drug discovery project where our aim is to interfere with some PPIs, we could obtain binding of drug-like fragments in several potentially interesting pockets on our target. We would like to make a projection on how promising these individual pockets are. One way of doing this is through the Sitemap program (Halgren, T. A. Identifying and characterizing binding sites and assessing druggability. J. Chem. Inf. Model 49, 377–389 (2009)). Are there other tools around to do this? In particular, we would like to have accurate numbers for the pocket volume, surface, no. of H-bond donors and acceptors, average hydrophobicity, etc etc. Thank you, Sergei Prof. Sergei V. Strelkov Laboratory for Biocrystallography Department of Pharmaceutical Sciences, KU Leuven O&N2, Campus Gasthuisberg, Herestraat 49 bus 822, 3000 Leuven, Belgium Phone: +32 16 33 08 45, mobile: +32 486 29 41 32 Lab pages: http://pharm.kuleuven.be/Biocrystallography<http://pharm.kuleuven.be/anafar> ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
