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Calculation of Protein-Ligand Interaction Energies by a Fragmentation Approach Combining High-Level Quantum Chemistry with Classical Many-Body Effects
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Quantum Chemistry.
2009 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, no 32, 11085-11094 p.Article in journal (Refereed) Published
Abstract [en]

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%.

Place, publisher, year, edition, pages
2009. Vol. 113, no 32, 11085-11094 p.
National Category
Chemical Sciences
URN: urn:nbn:se:uu:diva-145696DOI: 10.1021/jp810551hOAI: oai:DiVA.org:uu-145696DiVA: diva2:396615
Available from: 2011-02-10 Created: 2011-02-10 Last updated: 2011-10-06Bibliographically approved

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Aquilante, Francesco
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