Speaker: Dr. Eric Darve
From: Department of Mechanical Engineering, Stanford University
Date / Time / Room: Tuesday, March 28, 2006 / 4:00 PM / 120 DeBartolo Hall
Tea: 3:30 PM

Title:Computing Free Energy Using Thermodynamic Integration

Abstract: The adaptive biasing force method is an efficient technique to compute the potential of mean force along a reaction coordinate and for alchemical transformations. We present recent developments of the method for vector free energy calculations (i.e. for several reaction coordinates or for multiple alchemical transformations). General formulas are derived and theirrelative merit is discussed. Our approach will be compared with other popular techniques such as metadynamics. Application examples will be provided for simple examples, such as alanine dipeptide, and a more advanced one: the insertion of an amphipathic helix inside a cell membrane. For the latter, we will examine the stability of the inserted peptide relative to the interfacial configuration and its role in the association of individual peptides into larger multimeric structures, such as cellular channels. Our candidate for studies is the synthetic peptide (LSLLLSL)3. It was shown experimentally that, in the presence of an electric field, the orientation changes from parallel to the membrane to perpendicular and the location of the center-of-mass (COM) changes from the membrane surface to the center of the lipid bilayer. Experimental results, however, provide no information about stability of individual helices in the transmembrane orientation.