Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Homology Modeling and Molecular Dynamics Simulations of RNA Polymerases
Although transcription is of central importance to cell survival, only few antimicrobial agents have been directed towards the RNA polymerase (RNAP) enzyme. Rifampicin, one of the most potent and broad spectrum antibiotics and a key component of anti-tuberculosis therapy, binds in a pocket of the RNAP deep within the DNA/RNA channel, but more than 12 Å away from the active site. Unfortunately, binding of Rifampicin can be easily disturbed by enzyme mutations. Therefore, we are interested in blocking of active sites of bacterial RNAPs directly using analogs of NTPs. Such approach was found as very potent in the case of viral infections. Here, we present results of homology modeling (using the MODELLER software package), ab initio and QMMM calculations (GAUSSIAN03, ONIOM) and classical molecular dynamics simulations (AMBER and NAMD software packages). RNAPs in complex with nucleic acids (template DNA strand, RNA transcript, NTPs - either natural or chemically modified) were investigate in detail.
Support from the Ministry of Education, Youth and Sports of the Czech Republic (Project No. MSM 0021620835 and Project No. NPVII 2B06065) is gratefully acknowledged.