Sunday, February 8, 2015
159a
795-Pos Board B575
CHARMM Gui Membrane Builder Updates
Xi Cheng, Yifei Qi, Jumin Lee, Sunhwan Jo, Wonpil Im.
reference to the experimental data, under the so-called maximum entropy prin-
ciple. Recent practical formulations of this approach involve simulations car-
ried out over multiple replicas or iterative ensemble-correction procedures
based on the determination of several (Lagrange) parameters. Here, we present
an alternative, self-learning approach to sample molecular ensembles compat-
ible with experimental data with the minimal possible bias on the simulation
trajectories. The method does not require multiple replicas and is based on
adding an adaptive bias potential during the simulation that discourages the
sampling of conformations that are not consistent with the experimental mea-
surements. To illustrate this approach, we applied this novel simulation tech-
nique to spin-labeled T4-lysozyme, targeting a set of spin-spin distance
distributions measured by DEER/EPR spectroscopy. We show how the pro-
posed method is able to efficiently sample the experimental distance distribu-
tions without altering uncorrelated degrees of freedom. We anticipate that
this new simulation approach will be widely useful to obtain conformational
ensembles compatible with diverse types of experimental measurements of bio-
molecular dynamics.
Center for bioinformatics, The university of kansas, Lawrence, KS, USA.
designed to generate various molecular simulation systems and input files to
facilitate and standardize the usage of common and advanced simulation
through an automated optimized process. We have made a significant amount
of efforts to implement basic and common molecular dynamics simulation
techniques into web interface and the web interface has generated a multitude
of positive feedback from our users. In this work, we describe our latest efforts
to bringing more advanced molecular modeling and simulation techniques to
the web interface, including (1) HMMM builder establishing the high mobile
membrane-mimetic model, (2) martini maker building coarse-grain models
in Martini force fields, (3) NAMD, GROMACS, OpenMM equilibration and
production inputs.
796-Pos Board B576
Experimental and Theoretical Approaches to the Study of Probe Diffusion
in Macromolecular Solutions
792-Pos Board B572
Efficient High Accuracy Non-Bonded Interactions in the CHARMM
Simulation Package
Frank C. Pickard, Andrew Craig Simmonett, Bernard Rigoberto Brooks.
Laboratory of Computational Biology, National Institutes of Health,
Rockville, MD, USA.
Most molecular dynamics simulations are carried out using isotropic atom-
atom potentials to model non-bonded interactions. Such potentials can be
insufficient to accurately model a variety of physical properties present in
biologically relevant molecules. A proper description of the anisotropy of the
electrostatic interactions is of particular importance, as it directly affects a
variety of structural and transport properties such as hydrogen bonding and
diffusion. We have recently developed a novel, algorithm to efficiently calcu-
late coulombic forces in the CHARMM simulation package using an arbitrary
order multipole expansion. Further work has extended this algorithm to effi-
ciently account for dipolar polarization and dispersion. We present details of
the algorithm, its implementation and initial calculations on condensed phase
water enabled by this work.
Preston Donovan1, Yasaman Chehreghanianzabi2, Muruhan Rathinam1,
Silviya Zustiak2.
1Mathematics and Statistics, University of Maryland Baltimore County,
Baltimore, MD, USA, 2Biomedical Engineering, Saint Louis University,
Saint Louis, MO, USA.
Diffusion in macromolecular solutions and networks is a topic of vast impor-
tance in many fields related to medical devices, biotechnology, tissue engineer-
ing, or drug delivery. Thus, effort has been devoted to developing techniques
for measuring and models for predicting diffusion in macromolecular solutions
and networks. However, very few techniques are capable of probing diffusion
in situ, real time, and non-invasively and while many models of diffusion exist,
all of them have their drawbacks. Ideally a model starting from basic physics
using rigorous mathematical principles should be developed that is also sup-
ported by experimental findings.
First, we present measurements of probe diffusion in polymeric solutions
conducted by Fluorescence Correlation Spectroscopy (FCS). We have shown
that FCS is an excellent tool for real time, non-invasive study of diffusion
in complex media. Here, we present studies identifying several transport
regimes – without interaction, and with interaction between the probe and
the macromolecule. In the latter regime the nature of the interaction deter-
mines the specifics of the sub-diffusional process. We discuss two interaction
examples – one where a ‘‘permanent’’ polymer/probe complex is formed,
and one where ionic interaction is responsible for the decrease in probe
diffusivity.
We have also developed a novel mathematical model based on homogenization
theory, to describe the effective diffusion process. To the best of our knowl-
edge, homogenization theory, has not been used previously to describe the
diffusion of probes in macromolecular solutions. The homogenization theory
was confirmed by Monte Carlo simulations. An excellent agreement between
the homogenization theory and Monte Carlo simulations as well as comparison
to experimental data provided evidence for the utility of the homogenization
theory for predicting diffusion in macromolecular solutions.
793-Pos Board B573
Towards a Polarizable Force Field for RNA based on the Classical Drude
Oscillator
Justin A. Lemkul, Alexey Savelyev, Alexander D. MacKerell, Jr.
Pharmaceutical Sciences, University of Maryland, Baltimore, Baltimore,
MD, USA.
RNA plays many important roles in the cell, including information transfer,
gene regulation, protein synthesis, and catalysis. This diversity in function
arises in part from the adoption of complex tertiary structures and interconver-
sion between multiple conformational states in response to bound metabolites
or changes in other cellular conditions. Modeling RNA with atomistic resolu-
tion using molecular dynamics (MD) simulations requires a high-quality empir-
ical force field that can adequately describe the properties of both canonical and
non-canonical structures and is sensitive to environmental conditions. To this
end, we are developing a force field for RNA that includes the explicit treat-
ment of electronic polarization using the classical Drude Oscillator model.
Optimization is focused on the RNA 20-hydroxyl group and the phosphodiester
backbone targeting 2-D quantum mechanical (QM) potential energy and dipole
moment surfaces in combination with condensed phase MD simulations of both
canonical and non-canonical RNA structures. Parameter validation involves
conducting MD simulations of various RNAs not included in the training set.
797-Pos Board B577
A Coupled Two-Dimensional Main Chain Torsional Potential for Protein
Dynamics
Ya Gao1, Yongxiu Li1, John Z.H. Zhang1,2, Ye Mei1,2
.
1State Key Laboratory of Precision Spectroscopy, East China Normal
University, Shanghai, China, 2NYU-ECNU Center for Computational
Chemistry at NYU Shanghai, Shanghai, China.
794-Pos Board B574
Implementation of Replica-Exchange Umbrella Sampling to the DFTBD
Simulation Package
Shingo Ito, Yuko Okamoto, Stephan Irle.
A new AMBER compatible force field is proposed for balanced representation
of secondary structures. In this modified AMBER force field (AMBER2D), the
main chain torsion energy is represented by 2-dimensional Fourier expansions
with parameters fitted to the potential energy surface generated by quantum
mechanical calculations of small peptides in solution at M06 2X/aug-cc-
pvtz//HF/6-31G** level. Solvation model based on solute electron density
(SMD) developed in Truhlar’s group was considered. The benchmark systems
used in the validation of this force field include capped dipeptides (Ace-X-
NME, XP), tripeptides (XXX, XA, G, V}; GYG, Y {A, V, F, L, S, E, K,
M}), alanine tetrapeptide, Ac-(AAQAA)3 -NH2, and ubiquitin. Besides, we
also investigate the folding of two representative proteins (PDB ID 2I9M
and 1LE1). The results demonstrated that this 2D main chain torsion is effec-
tive in delineating the energy variation associated with main chain torsions.
Furthermore, the electrostatic polarization effect is very important for long pep-
tides or proteins. This work also serves as an implication for the necessity of
Nagoya University, Nagoya, Japan.
We have investigated the computational methods which combined the self-
consistent-charge Density Functional based Tight Binding (DFTB) method
[1] for fast calculations of quantum effects and the Replica-Exchange Umbrella
Sampling (REUS)[2] for enhanced conformational sampling. One of the excel-
lent QM-MD simulation package named DFTBþ does not have REUS method
incorporated. We thus modified DFTBþ to include the REUS method. We will
compare the results of DFTBþ calculations with those by another simulation
package. We will present the two comparative results for proton transfer reac-
tions in small molecules.
[1] M. Elstner, D. Porezag, G. Jungnickel, J. Elsner, M. Haugk, Th. Frauen-
heim, S. Suhai, and G. Seifert, Phys. Rev. B 58, 7260 (1998).
[2] Y. Sugita, A. Kitao, and Y. Okamoto, J. Chem. Phys. 113, 6042 (2000).
Jin, Qiaomei
