|
 ABSTRACT
Electrostatic interactions play a significant role in determining the binding affinity of molecules and drugs. While significant effort has been devoted to the accurate computation of biomolecular electrostatics based on an all-atomic solution of the Poisson-Boltzmann (PB) equation for smaller proteins and nucleic acids, relatively little has been done to optimize the efficiency of electrostatic energetics and force computations of macromolecules at varying resolutions (also called coarse-graining). We have developed an efficient and comprehensive framework for computing coarse-grained PB electrostatic potentials, polarization energetics and forces for smooth multi-resolution representations of almost all molecular structures, available in the PDB. Important aspects of our framework include the use of variational methods for generating C2-smooth and multi-resolution molecular surfaces (as dielectric interfaces), a parameterization and discretization of the PB equation using an algebraic spline boundary element method, and the rapid estimation of the electrostatic energetics and forces using a kernel independent fast multipole method. We present details of our implementation, as well as several performance results on a number of examples.
REFERENCES
Note: OCR errors may be found in this Reference List extracted from the full text article. ACM has opted to expose the complete List rather than only correct and linked references.
| |
1
|
A. H. Juffer, E. Botta, B. van Keulen, A. van der Ploeg, and H. Berensen. J Chemical Physics, 97:144--171, 1991.
|
| |
2
|
A. Arkhipov, P. Freddolino, K. Imada, K. Namba, and K. Schulten. Biophy. J., 91:4589--4597, 2006.
|
| |
3
|
I. Bahar and R. Jernigan. J. Mol. Biol., 266:195--214, 1997.
|
| |
4
|
C. Bajaj and S.-C. A. Chen. SIAM Journal on Scientific Computing, submitted, 2009.
|
| |
5
|
C. Bajaj, G. Xu, and Q. Zhang. Journal of Computer Science and Technology, 23(6):1026--1036, 2008.
|
| |
6
|
C. Bajaj and W. Zhao. SIAM Journal on Scientific Computing, under review, 2009.
|
| |
7
|
C. Bajaj, W. Zhao, S.-C. A. Chen, G. Xu, and Q. Zhang. ICES Report, 2009.
|
| |
8
|
N. Basdevant, D. Borgis, and T. Ha-Duong. J. Phys. Chem. B, 111:9390--9399, 2007.
|
| |
9
|
R. Bharadwaj, A. Windemuth, S. Sridharan, B. Honig, and A. Nicholls. J. Comput Chem., 16:898, 1995.
|
| |
10
|
A. J. Bordner and G. A. Huber. J. Comput Chem., 24:353--367, 2003.
|
| |
11
|
A. H. Boschitsch, M. O. Fenley, and H.-X. Zhou. J. Phys. Chem., 106:2741--2754, 2002.
|
| |
12
|
N.-V. Buchete, J. Straub, and D. Thirumalai. Protein Sci., 13:862--874, 2004.
|
| |
13
|
M. Connolly. J. Appl. Cryst., 16:548--558, 1983.
|
| |
14
|
M. K. Gilson, M. E. Davis, B. A. Luty, and J. McCammon. J. Phys. Chem., 97:3591--600, 1993.
|
| |
15
|
B. Z. Lu and J. A. McCammon. J. Chem. Theory Comput., 3:1134--1142, 2007.
|
| |
16
|
D. Marquardt. J. Soc. Indust. Appl. Math., 11:431--441, 1963.
|
| |
17
|
K. A. Sharp and B. Honig. J. Phys. Chem., 94:7684--7692, 1990.
|
| |
18
|
A. Smith and C. Hall. Proteins: Structure, function, and genetics, 44:344--360, 2001.
|
| |
19
|
W. C. Still, A. Tempczyk, R. C. Hawley, and T. Hendrickson. J. Am. Chem. Soc, 112:6127--6129, 1990.
|
| |
20
|
Y. Ueeda, H. Taketomi, and N. Gō. Biopolymers, 17:1531--1548, 1978.
|
| |
21
|
G. Xu and Q. Zhang. Mathematica Numerica Sinica, 28(4):337--356, 2006.
|
| |
22
|
L. Ying, G. Biros, and D. Zorin. Journal of Computational Physics, 196(2):591--626, 2004.
|
| |
23
|
R. Zauhar and R. Morgan. J. Mol. Biol., 186:815--820, 1985.
|
| |
24
|
W. Zhao, G. Xu, and C. Bajaj. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2009.
|
|
Adobe Acrobat
QuickTime
Windows Media Player
Real Player
Pdf