TITLE

Electrostatic Clustering and Free Energy Calculations Provide a Foundation for Protein Design and Optimization

AUTHOR(S)
Gorham, Ronald; Kieslich, Chris; Morikis, Dimitrios
PUB. DATE
April 2011
SOURCE
Annals of Biomedical Engineering;Apr2011, Vol. 39 Issue 4, p1252
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Electrostatic interactions are ubiquitous in proteins and dictate stability and function. In this review, we discuss several methods for the analysis of electrostatics in protein-protein interactions. We discuss alanine-scanning mutagenesis, Poisson-Boltzmann electrostatics, free energy calculations, electrostatic similarity distances, and hierarchical clustering of electrostatic potentials. Our recently developed computational framework, known as Analysis of Electrostatic Similarities Of Proteins (AESOP), incorporates these tools to efficiently elucidate the role of electrostatic potentials in protein interactions. We present the application of AESOP to several proteins and protein complexes, for which charge is purported to facilitate protein association. Specifically, we illustrate how recent work has shaped the formulation of electrostatic calculations, the correlation of electrostatic free energies and electrostatic potential clustering results with experimental binding and activity data, the pH dependence of protein stability and association, the design of mutant proteins with enhanced immunological activity, and how AESOP can expose deficiencies in structural models and experimental data. This integrative approach can be utilized to develop mechanistic models and to guide experimental studies by predicting mutations with desired physicochemical properties and function. Alteration of the electrostatic properties of proteins offers a basis for the design of proteins with optimized binding and activity.
ACCESSION #
59698833

 

Related Articles

  • Kinetoplastid RNA editing ligases 1 and 2 exhibit different electrostatic properties. Alireza Shaneh; Reza Salavati // Journal of Molecular Modeling;Jan2010, Vol. 16 Issue 1, p61 

    Abstract  Kinetoplastid RNA editing ligases 1 and 2 (KREL1 and KREL2) share a significant degree of sequence homology. However, biochemical experiments have reported that KREL1 and KREL2 differ in their functional roles during the RNA editing process. In this study, we hypothesize that...

  • Internal force field in proteins seen by divergence entropy. Marchewka, Damian; Banach, Mateusz; Roterman, Irena // Bioinformation;2011, Vol. 6 Issue 8, p300 

    The characteristic distribution of non-binding interactions in a protein is described. It establishes that hydrophobic interactions can be characterized by suitable 3D Gauss functions while electrostatic interactions generally follow a random distribution. The implementation of this observation...

  • Constraining density functional approximations to yield self-interaction free potentials. Gidopoulos, Nikitas I.; Lathiotakis, Nektarios N. // Journal of Chemical Physics;6/14/2012, Vol. 136 Issue 22, p224109 

    Self-interactions (SIs) are a major problem in density functional approximations and the source of serious divergence from experimental results. Here, we propose to optimize density functional total energies in terms of the effective local potential, under constraints for the effective potential...

  • Reassessment of the Unique Mode of Binding between Angiotensin II Type 1 Receptor and Their Blockers. Miura, Shin-Ichiro; Nakao, Naoki; Hanzawa, Hiroyuki; Matsuo, Yoshino; Saku, Keijiro; Karnik, Sadashiva S. // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    While the molecular structures of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are very similar, they are also slightly different. Although each ARB has been shown to exhibit a unique mode of binding to AT1 receptor, different positions of the AT1 receptor have been analyzed and...

  • O(N3) scaling of two-electron integrals during molecular geometry optimization. Ionova, Irina V.; Carter, Emily A. // Journal of Chemical Physics;5/1/1994, Vol. 100 Issue 9, p6562 

    We propose an optimization technique designed specifically for molecular structure optimization performed on an ab initio level. This gradient-based technique is a modification of quadratically convergent quasi-Newton method, and although it requires more energy evaluations than the conventional...

  • Optimization of the Probe-Forming System for a Scanning Nuclear Microprobe Based on the ÉGP-10 Electrostatic Tandem Accelerator. Abramovich, S.N.; Zavjalov, V.N.; Zvenigorodsky, A.G.; Ignat'ev, I.G.; Magilin, D.V.; Melnik, K.I.; Ponomarev, A.G. // Technical Physics;Feb2005, Vol. 50 Issue 2, p146 

    The probe-forming system of a nuclear scanning microprobe based on the parametric multiplets of quadrupole lenses is optimized. The optimization is aimed at creating an ion probe with energy of several MeV that produces a micrometer spot on the target at a current of ∼100 pA. The influence...

  • Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Zhu, Tingting; Wang, Ping; Wang, Li; Sun, Chang; Tian, Yuan; Li, Jie; Xu, Yanhui; Roundtree, Ian A; Wang, Xiao; He, Chuan // Cell Research;Dec2014, Vol. 24 Issue 12, p1493 

    A letter to the editor is presented regarding the structure of the binding protein of the YTH domain found in Ribose nucleic acid (RNA).

  • A strategy for reducing gross errors in the generalized Born models of implicit solvation. Onufriev, Alexey V.; Sigalov, Grigori // Journal of Chemical Physics;4/28/2011, Vol. 134 Issue 16, p164104 

    The 'canonical' generalized Born (GB) formula [C. Still, A. Tempczyk, R. C. Hawley, and T. Hendrickson, J. Am. Chem. Soc. 112, 6127 (1990)] is known to provide accurate estimates for total electrostatic solvation energies ΔGel of biomolecules if the corresponding effective Born radii are...

  • Beam instrumentation for the Ultra-low energy Storage Ring (USR). Panniello, M.; Kühnel, K.; Papash, A.; Harasimowicz, J.; Putignano, M.; Siggel-King, M.; Welsch, Carsten // Hyperfine Interactions;Dec2012, Vol. 213 Issue 1-3, p191 

    The electrostatic Ultra-low energy Storage Ring (USR) at the future Facility for Low energy Antiproton and Ion Research (FLAIR) will make available antiprotons from 300 keV down to 20 keV beam energy. This multipurpose machine puts challenging demands on the beam instrumentation due to the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics