Towards the Multiscale Modeling of Biological Systems and Processes –  i) RNA Polymerase and Transcription  ii) Dynamic Water Bridges in Electron  Transfer between Proteins 

Prof. Dennis R. Salahub                                              Fellow of the Royal  Society of Canada                                              Fellow of the American  Association for the Advancement of Science  

Abstract:

      One viewpoint (as expressed by Sui  Huang) of the still emerging field of systems biology sees integration along an  axis involving system size (and perhaps some dynamics) going from macromolecules  (proteins, DNA, RNA, etc) to cells, to tissues, to organs, to organisms, etc.  This is sometimes called computational biology. Another axis looks at kinetic  models at growing levels of complexity going from pathways, to modules to full  genetic regulatory networks. This is taken to lie in the general field of  bioinformatics.  There is an almost unpopulated chasm between the two  communities pursuing these two approaches.
      In this lecture I will argue  that a multiscale approach is necessary, with a starting point at even a finer  level of resolution, if one is to fill the gap between the two axes. I will try  to illustrate this with selected results from two different projects, both of  which involve Density Functional Theory (DFT), along with other methods.  
      The first part of the talk will focus on the mechanism of  transcription involving metallo-proteins with Mg ions in the active site. The  project uses DFT, MD (CHARMM), QM/MM (CHARMM-deMon) and the  ReaxFF Force Field, along with KMC simulations. We hope, in the fullness of  time, to be able to feed calculated information on reaction rates into the  Gillespie algorithm and, hence, have the behavior of the regulatory network  guided by the underlying atomistic and electronic mechanisms, and vice-versa in  a bottom-up – top-down approach to the problem. 
      The second part will  focus on electron transfer. Cellular energy production depends on electron  transfer (ET) between proteins. The identification of molecular dynamical  features during interprotein ET is essential to an understanding of the  molecular machinery of life. Here we perform a tunneling pathway analysis on  molecular dynamics simulations of the methylamine dehydrogenase—amicyanin redox  pair. We find that the most frequently occurring molecular configurations afford  superior electronic coupling, via a hydrogen-bonded “water bridge” between donor  and acceptor. Surface amino acid residues are crucial to the recognition and  dynamic docking of the proteins as well as the organisation of the aqueous  environment at the active site, increasing the lifetime of the water bridge.  Mutant complexes fail to achieve the same bridge stability and therefore suffer  from reduced electronic coupling, consistent with recent experimental findings.  I will report progress on understanding the effects of quantum  decoherence. 

时间: 2010年10月27日下午 3: 00

地址: 物理馆323

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四川大学物理科学与技术学院

2010-10-12