Well, there is almost nothing left to suggest, but one. Try co-crystallizing. While in solution molecules will have more flexibility to adopt a conformation that fits ligand bound state better. When soaking there might be restrictions on conformational changes needed for better binding due to already packed interactions. What you see in soaked-in crystals could be an incomplete bound state.
Just an idea. Vaheh From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> On Behalf Of <Shymaa Damfo> Sent: Saturday, March 5, 2022 3:01 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] ligand binds to one molecule Hello all, In homo-dimeric or homo-oligomeric protein crystal structures, what would be the reason for having a ligand (chemical compound or fragment) binds to one molecule and not all molecules in the asymmetric unit? I have soaked a fragment that has an affinity of 200 uM to a viral protein but I can only see it binds to one molecule (we have eight molecules in the AU). This is was also notable as well in some published PDB (dimeric protein). Any suggestions? Best wishes, Shymaa ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1<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<http://www.jiscmail.ac.uk/CCP4BB>, a mailing list hosted by www.jiscmail.ac.uk<http://www.jiscmail.ac.uk>, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/<https://www.jiscmail.ac.uk/policyandsecurity> ######################################################################## 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/
