Advanced

Calculation of Protein-Ligand Interaction Energies by a Fragmentation Approach Combining High-Level Quantum Chemistry with Classical Many-Body Effects

Söderhjelm, Pär LU ; Aquilante, Francesco and Ryde, Ulf LU (2009) In The Journal of Physical Chemistry Part B 113(32). p.11085-11094
Abstract
We have developed a method to estimate accurate interaction energies between a full protein and a bound ligand. It is based oil the recently proposed PMISP (polarizable multipole interaction with supermolecular pairs) method (Soderhjelm, P.; Ryde, U. J. Phys. Chem. A 2009, 113. 617), which treats electrostatic interaction by multipoles up to quadrupoles, induction by anisotropic polarizabilities, and nonclassical interactions by explicit quantum mechanical (QM) calculations, using a fragmentation approach. For a whole protein, electrostatics and induction are treated the same way, but for the nonclassical interactions, a Lennard-Jones term from a standard molecular mechanics (MM) force field (e.g., Amber) is used outside a certain distance... (More)
We have developed a method to estimate accurate interaction energies between a full protein and a bound ligand. It is based oil the recently proposed PMISP (polarizable multipole interaction with supermolecular pairs) method (Soderhjelm, P.; Ryde, U. J. Phys. Chem. A 2009, 113. 617), which treats electrostatic interaction by multipoles up to quadrupoles, induction by anisotropic polarizabilities, and nonclassical interactions by explicit quantum mechanical (QM) calculations, using a fragmentation approach. For a whole protein, electrostatics and induction are treated the same way, but for the nonclassical interactions, a Lennard-Jones term from a standard molecular mechanics (MM) force field (e.g., Amber) is used outside a certain distance from the ligand (4-7 angstrom). This QM/MM variant of the PMISP method is carefully tested by varying this distance. Several approximations related to the classical interactions are also evaluated. It is found that one can speed up the calculation by using density functional theory to compute multipoles and polarizabilities but that a proper treatment of polarization is important. As a demonstration of the method, the interaction energies of two ligands bound to avidin are calculated at the MP2/aug-cc-pVTZ level, with an expected relative error of 1-2%. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
113
issue
32
pages
11085 - 11094
publisher
The American Chemical Society
external identifiers
  • wos:000268661100007
  • scopus:68649091295
ISSN
1520-5207
DOI
10.1021/jp810551h
language
English
LU publication?
yes
id
715bb923-18c8-4a58-8978-77aa019b4ca4 (old id 1459896)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19618955?dopt=Abstract
date added to LUP
2009-08-25 14:48:43
date last changed
2017-07-30 03:58:39
@article{715bb923-18c8-4a58-8978-77aa019b4ca4,
  abstract     = {We have developed a method to estimate accurate interaction energies between a full protein and a bound ligand. It is based oil the recently proposed PMISP (polarizable multipole interaction with supermolecular pairs) method (Soderhjelm, P.; Ryde, U. J. Phys. Chem. A 2009, 113. 617), which treats electrostatic interaction by multipoles up to quadrupoles, induction by anisotropic polarizabilities, and nonclassical interactions by explicit quantum mechanical (QM) calculations, using a fragmentation approach. For a whole protein, electrostatics and induction are treated the same way, but for the nonclassical interactions, a Lennard-Jones term from a standard molecular mechanics (MM) force field (e.g., Amber) is used outside a certain distance from the ligand (4-7 angstrom). This QM/MM variant of the PMISP method is carefully tested by varying this distance. Several approximations related to the classical interactions are also evaluated. It is found that one can speed up the calculation by using density functional theory to compute multipoles and polarizabilities but that a proper treatment of polarization is important. As a demonstration of the method, the interaction energies of two ligands bound to avidin are calculated at the MP2/aug-cc-pVTZ level, with an expected relative error of 1-2%.},
  author       = {Söderhjelm, Pär and Aquilante, Francesco and Ryde, Ulf},
  issn         = {1520-5207},
  language     = {eng},
  number       = {32},
  pages        = {11085--11094},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Calculation of Protein-Ligand Interaction Energies by a Fragmentation Approach Combining High-Level Quantum Chemistry with Classical Many-Body Effects},
  url          = {http://dx.doi.org/10.1021/jp810551h},
  volume       = {113},
  year         = {2009},
}