Analysis of fast boundary-integral approximations for modeling electrostatic contributions of molecular binding

• Autorzy: Amelia B. Kreienkamp , Lucy Y. Liu , Mona S. Minkara , Matthew G. Knepley , Jaydeep P. Bardhan , Mala L. Radhakrishnan
• Języki publikacji: EN

Abstrakty

EN

We analyze and suggest improvements to a recently developed approximate continuum-electrostatic model for proteins. The model, called BIBEE/I (boundary-integral based electrostatics estimation with interpolation), was able to estimate electrostatic solvation free energies to within a mean unsigned error of 4% on a test set of more than 600 proteins¶a significant improvement over previous BIBEE models. In this work, we tested the BIBEE/I model for its capability to predict residue-by-residue interactions in protein–protein binding, using the widely studied model system of trypsin and bovine pancreatic trypsin inhibitor (BPTI). Finding that the BIBEE/I model performs surprisingly less well in this task than simpler BIBEE models, we seek to explain this behavior in terms of the models’ differing spectral approximations of the exact boundary-integral operator. Calculations of analytically solvable systems (spheres and tri-axial ellipsoids) suggest two possibilities for improvement. The first is a modified BIBEE/I approach that captures the asymptotic eigenvalue limit correctly, and the second involves the dipole and quadrupole modes for ellipsoidal approximations of protein geometries. Our analysis suggests that fast, rigorous approximate models derived from reduced-basis approximation of boundaryintegral equations might reach unprecedented accuracy, if the dipole and quadrupole modes can be captured quickly for general shapes.

Słowa kluczowe

EN

Component analysis; boundary-element methods; BIBEE; molecular electrostatics; continuum solvation; implicitsolvent models

Kategorie tematyczne

• 65N80: Fundamental solutions, Green's function methods, etc.
• 92C05: Biophysics
• 92C40: Biochemistry, molecular biology
• 65N38: Boundary element methods

• Wydawca: De Gruyter Open
• Czasopismo: Molecular Based Mathematical Biology
• Rocznik: 2013
• Tom: 1
• Strony: 124-150

Daty

otrzymano

2012-10-08

zaakceptowano

2013-04-29

online

2013-06-10

Twórcy

autor

Amelia B. Kreienkamp

autor

Lucy Y. Liu

autor

Mona S. Minkara

autor

Matthew G. Knepley

autor

Jaydeep P. Bardhan

autor

Mala L. Radhakrishnan

Bibliografia

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Identyfikatory

DOI

10.2478/mlbmb-2013-0007