Bulletin of the American Physical Society
2008 APS March Meeting
Volume 53, Number 2
Monday–Friday, March 10–14, 2008; New Orleans, Louisiana
Session J6: Effective Potentials and Force Fields for Simulating Biological Macromolecules |
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Sponsoring Units: DCOMP Chair: Ronald Levy, Rutgers University Room: Morial Convention Center RO4 |
Tuesday, March 11, 2008 11:15AM - 11:51AM |
J6.00001: Artifact or reality? Force field issues in the simulation proteins and nucleic acids Invited Speaker: Access to ever-increasing computational power is providing the means to critically evaluate the performance of atomistic force fields of biomolecules. With greater sampling, and more detailed comparisons to experiment, limitations and artifacts in the applied simulation protocols and force fields can be discovered and ultimately overcome. Additionally, we are able to more carefully validate and assess the performance of the simulations in comparison with experiment. In this talk, we will outline our experiences in large-scale simulations of protein and nucleic acid systems in the context of the AMBER biomolecular simulation program. Issues related to salt and dihedral parameters will be highlighted in applications ranging from ligand-induced remodeling of dihydrofolate reductase and cytochrome P450 2B4 protein structures to large-scale decoy sets and NMR comparisons of various RNA structures. [Preview Abstract] |
Tuesday, March 11, 2008 11:51AM - 12:27PM |
J6.00002: Development of a polarizable force field based on the classical Drude oscillator Invited Speaker: Empirical force field development requires a systematic approach allowing for the development of a practical potential energy function and optimization of physically realistic parameters that reproduce a range of target data. Ongoing efforts in our laboratory include the development of a polarizable force field based on the classical Drude oscillator for a range of molecules representative of biological systems. A central theme in these efforts is the accurate treatment of both atomic interactions as well as condensed phase properties. To achieve this goal extensions of the energy function have been implemented and parameter optimization has been performed targeting a variety of quantum mechanical results and experimental condensed phase properties. An overview of these studies will be presented. [Preview Abstract] |
Tuesday, March 11, 2008 12:27PM - 1:03PM |
J6.00003: The AGBNP implicit solvent model: recent advances and applications to biological macromolecules Invited Speaker: The Analytical Generalized Born plus Non-Polar (AGBNP) model is an analytical implicit water model suitable for molecular dynamics simulations of small molecules and macromolecules. It is based on an analytical pairwise descreening implementation of the continuum dielectric Generalized Born (GB) model and a non-polar hydration free energy model. AGBNP computes the descreening scaling factors that account for atomic overlaps from the geometry of the solute rather than treating them as geometry-independent parameters fit to numerical or experimental data. The non-polar hydration free energy model is decomposed into a cavity component based on the solute surface area and a solute-solvent van der Waals dispersion energy estimator. The aim of the model is to achieve atomic-resolution accuracy for modelling the many biological systems in which global conformational features are regulated by small and localized control elements. Since its introduction AGBNP has been employed to study a variety of biological problems ranging from peptide conformational propensity and folding, protein allostery, conformational equilibria of protein-ligand complexes, binding affinity prediction, and, more recently, to intrinsically disordered proteins, protein aggregation, the design of virus vaccine carriers, and macromolecular X-ray structure refinement. Recent development work has focused on computational performance enhancements and on improving the accuracy of the model with respect to explicit solvent simulation results. By comparing the details of the solvent potentials of mean force of several peptides calculated with explicit and implicit solvation, we have identified some aspects of the AGBNP model in need of improvement. We are exploring several strategies to address them including the adoption of a molecular surface description of the solute volume, the modelling of high-occupancy hydration sites, and the optimization of the non-polar free energy model. [Preview Abstract] |
Tuesday, March 11, 2008 1:03PM - 1:39PM |
J6.00004: Atomic-level simulations of biomolecular systems with a modified Amber force field Invited Speaker: Experimental methods have been highly successful in determining 3-dimensional biomolecular structures. However, most approaches provide only time- or ensemble-averaged data, making it much more difficult to study the dynamic and energetic aspects of biological systems. Atomic-resolution simulations are highly complementary to experiments, and can provide data with unparalleled resolution in time and space. Due to the long timescales of biologically relevant events, as well as the complexity of the energy function, accurate and precise simulations remain highly computationally challenging. This seminar will highlight recent progress in both areas, illustrating how energy functions that have been trained on simple peptide models can be successfully used for the study of much more complex systems. We demonstrate that our newly trained energy parameters significantly reduce the secondary structure bias reported for previous Amber parameter sets. Applications of the parameters include studies of folding behavior of peptides and small proteins, and the dynamic behavior of larger biomolecular systems such as conformational changes during drug binding in HIV-1 protease. [Preview Abstract] |
Tuesday, March 11, 2008 1:39PM - 2:15PM |
J6.00005: Beyond force fields. QM/MM conformational searches in biomolecules using Replica Exchange molecular dynamics. Invited Speaker: Force fields have been extremely successful for our understanding of structure, energetics and dynamics of biomolecules. However, they neglect, for the most part, quantum effects such as charge transfer and polarization. In this talk I will present our work using our newly developed QM/MM interface in the program Amber, which can very efficiently treat small peptides in explicit solvent using a number of different semiempirical methods. We use Replica Exchange molecular dynamics to sample the surface properly and ensure convergence. A comparison of the conformational space sampled by different semiempirical methods in explicit water classical models will be presented. The computational results will be compared against NMR experiments. [Preview Abstract] |
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