freeEaccurate - Exploring the free-energy landscapes of...

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1 Exploring the free-energy landscapes of biological systems with steered molecular dynamics Guodong Hu and L. Y. Chen* Department of Physics, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249 We perform steered molecular dynamics (SMD) simulations and use the Brownian dynamics fluctuation-dissipation-theorem (BD -FDT) to accurately compute the free-energy profiles for several biophysical processes of fundamental importance: hydration of methane and cations, binding of benzene to T4-lysozyme L99A mutant, and permeation of water through aquaglyceroporin. For each system, the center-of-mass coordinates of the small molecule (methane, ion, benzene, and water, respectively) is steered (pulled) at a given speed over a period time, during which the system transitions from one macroscopic state/conformation (State A) to another one (State B). The mechanical work of pulling the system is measured during the process, sampling a forward pulling path. Then the reverse pulling is conducted to sample a reverse path from B back to A. Sampling a small number of forward and reverse paths, we are able to accurately compute the free-energy profiles for all the afore-listed systems that represent various important aspects of biological physics. The numerical results are in excellent agreements with the experimental data and/or other computational studies available in the literature. 82.20.Wt, 82.37.Rs, 05.60.Cd, 05.40.Jc, 05.70.Ln [email protected]
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2 I. Introduction Accurate computation of free-energy is of essential importance in quantitative studies of biological systems because most biophysical/chemical processes are driven by the free-energy gradients. 1-8 Methods to calculate free-energy differences between two states (conformations) A and B fall into two classes, equilibrium methods and, developed more recently, non-equilibrium methods. A recent review can be found in Ref. 6 . The equilibrium approaches such as the thermodynamic integration method require more computing resources because they are based on “full” sampling of the equilibrium ensembles involved in a given biophysical process. The non-equilibrium approaches exploit the stochastic dynamics of the system driven with some applied forces and aim to map out the free-energy landscape in terms of the potential of mean force (PMF). 9 The free-energy difference between States A and B is extracted from the measurements of work along the transition paths connecting the two states. In Refs. 10 , a non-equilibrium PMF type of approach has been developed on the basis of the Brownian dynamics fluctuation-dissipation theorems (BD-FDT) 11 , extracting the equilibrium free-energy differences from irreversible (non-equilibrium) work measurements in steered molecular dynamics (SMD) simulations 12 . The precision and efficiency of the BD-FDT approach have been demonstrated with the coil-helix transition of deca-alanine peptide.
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This note was uploaded on 12/13/2010 for the course GENETIK 12 taught by Professor Atillabasar during the Spring '10 term at Istanbul Technical University.

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freeEaccurate - Exploring the free-energy landscapes of...

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