10.6084/m9.figshare.9611288.v1 Xin Long Xin Long Ruxiao Zheng Ruxiao Zheng Meilin Liu Meilin Liu Chuanfang Wu Chuanfang Wu Jinku Bao Jinku Bao Identification potential inhibitors against the <i>Streptococcus</i> quorum-sensing signal pathway Taylor & Francis Group 2019 ATP-binding protein ComA Streptococcus molecular docking molecular dynamics virtual screening 2019-08-14 11:02:03 Dataset https://tandf.figshare.com/articles/dataset/Identification_potential_inhibitors_against_the_i_Streptococcus_i_quorum-sensing_signal_pathway/9611288 <p>Streptococcal infections are common in human and antibiotics are frequently prescribed in clinical practice. However, infections caused by drug-resistant strains are particularly difficult to treat using common antibiotics. Hence, there is an urgent need for new antibiotics. Quorum sensing is a regulatory mechanism involving cell communication that is thought to play an important role in various bacterial infections, including those caused by <i>Streptococcus</i>. The ATP-binding cassette transporter ComA of <i>Streptococcus</i> is essential for quorum-sensing signal production. The inhibition of the ComA peptidase domain (ComA PEP) suppresses the quorum-sensing pathway and resulting changes in phenotype and/or behavior. Using virtual screening and molecular dynamics simulations, two promising candidate compounds, ZINC32918029 and ZINC6751571, were found. These compounds had similar binding modes and interactions to the experimentally determined reference inhibitor 6CH. However, a significantly stronger negative binding energy was achieved (−113.501 ± 15.312 KJ/mol and −103.153 ± 11.912 KJ/mol for ZINC32918029 and ZINC6751571, respectively). Molecular dynamics simulations also revealed that ZINC32918029 and ZINC6751571 had a strong affinity for ComA PEP. These results indicate that ZINC32918029 and ZINC6751571 are promising candidate inhibitors of the <i>Streptococcus</i> quorum-sensing pathway.</p> <p>Communicated by Ramaswamy H. Sarma</p>