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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Protein folding simulation using temperature based cascade MD

Protein folding is a multi micro second time scale event and involves many conformational transitions. Large conformational transitions important for biological functions are difficult to capture using super-computers. Protein folding being a stochastic process witnesses these transition as rare events. Many new methodologies have been proposed for observing these rare events. In this work, Temperature based cascade MD (TcMD) is proposed as a technique to study the conformational transition without applying any external force. Engrailed homeodomain folding study has been carried out using Temperature based cascade MD where the unfolded structure of RMSD 20 Å folded to form a structure of RMSD 2.5 20 Å. Three sets of cascade MD runs were carried using implicit, explicit and implicit with charge updated conformation. In all the simulations the structure of 2.5 20 Å was reached within few nanoseconds using this method. Cascade MD was followed by Umbrella sampling using snapshots from Temperature based cascade MD simulation trajectory to build entire conformational transition pathway. Advantage of the method is that pathways for particular reaction can be explored within short duration of simulation time and disadvantage is that the knowledge of start and end state is required.

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Vinod Jani
Uddhavesh Sonavane
Rajendra Joshi

Bioinformatics Group
Centre for Development of Advanced Computing (C-DAC)
Pune 411 007 India Ph:+91-20-25694084
vinodj@cdac.in
rajendra@cdac.in