Bulletin of the American Physical Society
2006 APS March Meeting
Monday–Friday, March 13–17, 2006; Baltimore, MD
Session K7: New Methods and Algorithms for Biomolecular Modeling |
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Sponsoring Units: DBP Chair: Christopher Roland, North Carolina State University Room: Baltimore Convention Center 307 |
Tuesday, March 14, 2006 2:30PM - 3:06PM |
K7.00001: Adaptive Biasing Force Method for Vector Free Energy Calculations Invited Speaker: 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 their relative merit is discussed. In particular, many techniques require the ability to calculate second order derivatives and are therefore cumbersome to implement for complex reaction coordinates. We present new formulations requiring first derivatives only. 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. We will present results on the free energy surface of insertion of (LSLLLSL)$_3$ as a function of two coordinates: the distance of the COM of the peptide to the center of the membrane and the orientation of the helix relative to the membrane surface. Our results show that there is a global minimum corresponding to the parallel orientation at the water-membrane interface. The transmembrane arrangement of a single peptide is only metastable, i.e. it corresponds to a local minimum. [Preview Abstract] |
Tuesday, March 14, 2006 3:06PM - 3:42PM |
K7.00002: New Distributed Multipole Methods for Accurate Electrostatics for Large-Scale Biomolecular Simultations Invited Speaker: An accurate and numerically efficient treatment of electrostatics is essential for biomolecular simulations, as this stabilizes much of the delicate 3-d structure associated with biomolecules. Currently, force fields such as AMBER and CHARMM assign ``partial charges'' to every atom in a simulation in order to model the interatomic electrostatic forces, so that the calculation of the electrostatics rapidly becomes the computational bottleneck in large-scale simulations. There are two main issues associated with the current treatment of classical electrostatics: (i) how does one eliminate the artifacts associated with the point-charges (e.g., the underdetermined nature of the current RESP fitting procedure for large, flexible molecules) used in the force fields in a physically meaningful way? (ii) how does one efficiently simulate the very costly long-range electrostatic interactions? Recently, we have dealt with both of these challenges as follows. In order to improve the description of the molecular electrostatic potentials (MEPs), a new distributed multipole analysis based on localized functions -- Wannier, Boys, and Edminston-Ruedenberg -- was introduced, which allows for a first principles calculation of the partial charges and multipoles. Through a suitable generalization of the particle mesh Ewald (PME) and multigrid method, one can treat electrostatic multipoles all the way to hexadecapoles all without prohibitive extra costs. The importance of these methods for large-scale simulations will be discussed, and examplified by simulations from polarizable DNA models. [Preview Abstract] |
Tuesday, March 14, 2006 3:42PM - 4:18PM |
K7.00003: Flexibility in Biomolecules: Beyond Molecular Dynamics. Invited Speaker: Molecular dynamics is unable to explore the conformations large protein complexes, viral capsids etc. Using Lagrange constraints for covalent bonds, hydrogen bonds, hydrophobic tethers, and van der Waals excluded volumes, Monte Carlo dynamics uses ghost templates to efficiently guide rigid clusters via the flexible joints between them. The generation a new protein conformation typically requires about 100 milliseconds CPU time. Specifically, input from a single X-ray crystallographic structure can generate an ensemble of structures remarkably similar to those observed in NMR. Further applications are pathways for ligand docking, misfolding proteins and viral-capsid swelling. The software used for this work is available either interactively or for downloading via flexweb.asu.edu. \newline [Preview Abstract] |
Tuesday, March 14, 2006 4:18PM - 4:54PM |
K7.00004: Enhanced conformational sampling via novel variable transformations and very large time-step molecular dynamics Invited Speaker: One of the computational grand challenge problems is to develop methodology capable of sampling conformational equilibria in systems with rough energy landscapes. If met, many important problems, most notably protein folding, could be significantly impacted. In this talk, two new approaches for addressing this problem will be presented. First, it will be shown how molecular dynamics can be combined with a novel variable transformation designed to warp configuration space in such a way that barriers are reduced and attractive basins stretched. This method rigorously preserves equilibrium properties while leading to very large enhancements in sampling efficiency. Extensions of this approach to the calculation/exploration of free energy surfaces will be discussed. Next, a new very large time-step molecular dynamics method will be introduced that overcomes the resonances which plague many molecular dynamics algorithms. The performance of the methods is demonstrated on a variety of systems including liquid water, long polymer chains simple protein models, and oligopeptides. [Preview Abstract] |
Tuesday, March 14, 2006 4:54PM - 5:30PM |
K7.00005: Reaction Path Reaction path potential for complex biomolecular systems derived from mixed QM/MM methods Invited Speaker: The reaction path potential (RPP) follows the ideas from the reaction path Hamiltonian of Miller, Handy and Adams for gas phase reactions but is designed specifically for large systems described with QM/MM methods. RPP is an analytical energy expression of the combined QM/MM potential energy along the minimum energy path (J. Chem. Phys. 121, 89, 2004). An expansion around the minimum energy path is made in both the nuclear and the electronic degrees of freedom for the QM subsystem, while the interaction between the QM and MM subsystems is described as the interaction of the MM charges with polarizable QM charges. The input data for constructing the reaction path potential are energies, frequencies and electron density response properties of the QM subsystem. RPP provides a potential energy surface for rigorous statistical mechanics and mixed quantum/classical reaction dynamics calculations of complex systems, as will be shown for several enzymes. Recent further development in determining QM/MM free energy reaction paths will also be presented. [Preview Abstract] |
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