Binding of Calcium and Other Metal Ions to the EF-Hand Loops of Calmodulin Studied by Quantum Chemical Calculations and Molecular Dynamics Simulations

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• 作者：Martin Lep//pubs.acs.org/images/entities/scaron.gif" border="0">í ; k ; Martin J. Field
• 刊名：Journal of Physical Chemistry B
• 出版年：2007
• 出版时间：August 23, 2007
• 年：2007
• 卷：111
• 期：33
• 页码：10012 - 10022
• 全文大小：171K
• 年卷期：v.111,no.33(August 23, 2007)
• ISSN：1520-5207

文摘

Calcium ion binding by the four EF-hand motifs of the protein calmodulin (CaM) is a central event in Ca²⁺-based cellular signaling. To understand molecular details of this complex process, isolated Ca²⁺-binding loopscan be studied, by use of both experiments and calculations. In this work, we explore the metal specificity ofthe four Ca²⁺-binding loops of CaM using density functional theory (DFT) quantum chemical calculationsand molecular dynamics simulations. We study CaM complexes with the physiologically important ions ofcalcium (Ca²⁺) and magnesium (Mg²⁺) and also with two other ions, strontium (Sr²⁺) and lanthanum (La³⁺).The former is of interest in the area of radioactive waste bioremediation, whereas the latter is often used asa probe of Ca²⁺-binding sites. We obtain intrinsic metal ion-loop binding energies as well as theircomponents: vacuum, charge-transfer, solvation, entropy, and deformation terms. A detailed analysis of theresults reveals that the total binding energy depends on a delicate balance among these energy components.They, in turn, are determined by the cation's charge and size as well as the amino acid composition andflexibility of the loops and the identity of the metal-chelating residues.