itr/ap: tools and methods for multiscale biomolecular simulations pi: celeste sagui – dmr-0121361
DESCRIPTION
ITR/AP: Tools and Methods for Multiscale Biomolecular Simulations PI: Celeste Sagui – DMR-0121361 NC State, UNC, Duke. biomolecular simulations are notoriously difficult because they include long-range electrostatics, chemical reactions, water solvent, etc - PowerPoint PPT PresentationTRANSCRIPT
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ITR/AP: Tools and Methods for Multiscale Biomolecular Simulations
PI: Celeste Sagui – DMR-0121361
NC State, UNC, Duke
• biomolecular simulations are notoriously difficult because they include long-range electrostatics, chemical reactions, water solvent, etc
•ideally, one would like to use quantum mechanical methods
• given the very large number of atoms involved in a typical biomolecular simulation (>105), this is usually too costly
• aim of this grant is to produce tools to integrate different simulation methods
• schematic showing hierarchy of methods to be integrated
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Improved Electrostatics for Biomolecular Simulations
Sagui, Pomorski, Darden, Pedersen and Roland
NC State, UNC, and NIEHS
DMR-0121361
• greatest loss of accuracy in current classical biomolecular simulations is due to poor treatment of electrostatics
• electrostatics is absolutely essential to keep folded DNA and protein structures• new algorithms developed by group enables highly accurate simulations at reasonable computational costs
• improved description based on partitioning the molecular electronic cloud by means of a Wannier functions
• should lead to new generation of biomolecular simulations
ab initio WF result
Comparison of molecular electrostatic potential for water dimers outside van der Waals surface
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Mixed Quantum and Molecular Mechanics Simulations of Sulfuryl Transfer Reaction Catalyzed by Human Estrogen Sulfotransferase
P. Lin and L. Pedersen
• estrogen is one of the most important hormones found in the human body
• it is extremely important that the body regulate estrogen, being able to both turn it on and off
• the deactivation of estrogen takes place by means of transfering a sulfate group to the hormone
• the details of this important reaction were investigated by means of a mixed quantum and classical molecular dynamics simulation, as shown in the movie • movie shows how the sulfate
group gets placed on the estrogen
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Nitrogenase FeMo Cofactor: central ligand and reactions
Future plans
- identification of the site of nitrogen dimer binding and reaction- carrying out Car-Parrinello and with the breakthrough Continuous Quantum Monte Carlo [3] simulation of the reaction
Results
Fig. 1Fig. 2
Motivation
[1] O. Einsle, et al., Science, 297, 1696 (2002).[2] T. Lovell , et al., JACS, 125, 8377 (2003); I. Dance, Chem. Commun. , 324 (2003); [3] J.C. Grossman and L. Mitas, submitted
● The Nitrogenase enzyme catalyzes the transformation of N2 to
NH3 under ambient conditions (Fig. 1), with the active site being
the iron-molybdenum cofactor (FeMoco)
● Recent structural data by Einsle et al. [1] has shown the presence of new light atom inside the FeMoco cavity (C, N or O suggested).
● Full structural spin-restricted density functional optimization (Fig. 2) provided estimations of binding energies as E
b(O)<E
b(N)<E
b(C).
(1) Ordering of spin states with respect to energy is in accordance with [2].(2) Arguments based on geometry comparisons and redox potentials favor N as the most probable central ligand.
DMR-0121361