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Abstract
To model and simulate large molecular systems like proteins, the development of reduced representations is currently an active field of research. In a previous work [1], we developed an approach to locate minima and maxima in a smoothed molecular electrostatic potential (MEP) Φ, and applied it to the design of amino acid (AA) reduced point charge models (Fig. left). Such models were then used for the evaluation of the MEP of KcsA, a potassium ion channel structure. While efficient in approximating the corresponding all-atom MEP, the models however present two drawbacks. First, the points are located away from the skeleton of the structure, and second, their location and charge value may be dependent on the AA conformation.
In the present work, the approach is modified so as to determine the point charge centers from electron density (ED) distribution functions ρsm obtained using the Poisson equation:
Such a new procedure allows to overcome the two drawbacks mentioned above when extrema of ρ are located in distributions built on negative and positive charges separately (Fig. right). In this work, the charge values allowing the calculation of the initial MEP Φ are taken from the AMBER99 force field [2]. The new AA models allow to reproduce protein MEP maps, and additionally, provide solvation free energies obtained using the program APBS [3] that are in better agreement with the all-atom ones. Calculations were achieved on a set of 53 protein structures, listed in [4], and four KcsA channel structures (PDB access codes 1BL8, 2ATK, 2P7T, and 1S5H).
1. L. Leherte, D.P. Vercauteren, J. Chem. Theory Comput. 5 (2009) 3279-3298
2. J. Wang, P. Cieplak, P.A. Kollman, J. Comput. Chem. 21 (2000) 1049-1074
3. N.A. Baker, D. Sept, S. Joseph, M.J. Holst, J.A. McCammon, Proc. Natl. Acad. Sci. USA 98 (2001) 10037-10041
4. H. Tjong, H.-X. Zhou, J. Chem. Theory Comput. 4 (2008) 507-514
In the present work, the approach is modified so as to determine the point charge centers from electron density (ED) distribution functions ρsm obtained using the Poisson equation:
Such a new procedure allows to overcome the two drawbacks mentioned above when extrema of ρ are located in distributions built on negative and positive charges separately (Fig. right). In this work, the charge values allowing the calculation of the initial MEP Φ are taken from the AMBER99 force field [2]. The new AA models allow to reproduce protein MEP maps, and additionally, provide solvation free energies obtained using the program APBS [3] that are in better agreement with the all-atom ones. Calculations were achieved on a set of 53 protein structures, listed in [4], and four KcsA channel structures (PDB access codes 1BL8, 2ATK, 2P7T, and 1S5H).
1. L. Leherte, D.P. Vercauteren, J. Chem. Theory Comput. 5 (2009) 3279-3298
2. J. Wang, P. Cieplak, P.A. Kollman, J. Comput. Chem. 21 (2000) 1049-1074
3. N.A. Baker, D. Sept, S. Joseph, M.J. Holst, J.A. McCammon, Proc. Natl. Acad. Sci. USA 98 (2001) 10037-10041
4. H. Tjong, H.-X. Zhou, J. Chem. Theory Comput. 4 (2008) 507-514
Original language | English |
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Publication status | Published - Dec 2010 |
Event | Pacifichem 2010 - Honolulu, United States Duration: 15 Dec 2010 → … |
Symposium
Symposium | Pacifichem 2010 |
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Country/Territory | United States |
City | Honolulu |
Period | 15/12/10 → … |
Fingerprint
Dive into the research topics of 'Design of a reduced point charge model for proteins: Applications to molecular electrostatic potential and solvation energy calculations'. Together they form a unique fingerprint.Projects
- 1 Active
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Multiresolution analysis of molecular electrostatic potentials for proteins
21/01/08 → …
Project: Research
Activities
- 1 Participation in conference
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Pacifichem 2010
Laurence Leherte (Poster)
15 Dec 2010 → 20 Dec 2010Activity: Participating in or organising an event types › Participation in conference
Prizes
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Subvention "Agathon de Potter" pour participation au congrès Pacifichem 2010
Leherte, Laurence (Recipient), Dec 2010
Prize: Fellowship awarded competitively