Efficient Dynamic Protonation and Constant pH Simulations with Explicit Solvent: Calculation of Apparent pKa Values in Proteins
نویسندگان
چکیده
منابع مشابه
Constant pH Molecular Dynamics in Explicit Solvent with λ-Dynamics
pH is an important parameter in condensed-phase systems, because it determines the protonation state of titratable groups and thus influences the structure, dynamics, and function of molecules in solution. In most force field simulation protocols, however, the protonation state of a system (rather than its pH) is kept fixed and cannot adapt to changes of the local environment. Here, we present ...
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pH is a ubiquitous regulator of biological activity, including protein-folding, protein-protein interactions, and enzymatic activity. Existing constant pH molecular dynamics (CPHMD) models that were developed to address questions related to the pH-dependent properties of proteins are largely based on implicit solvent models. However, implicit solvent models are known to underestimate the desolv...
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Because of their central importance for understanding enzymatic mechanisms, pK(a) values are of great interest in biochemical research. It is common practice to determine pK(a) values of amino acid residues in proteins from NMR or FTIR titration curves by determining the pH at which the protonation probability is 50%. The pH dependence of the free energy required to protonate this residue is th...
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By utilizing Graphics Processing Units, we show that constant pH molecular dynamics simulations (CpHMD) run in Generalized Born (GB) implicit solvent for long time scales can yield poor pKa predictions as a result of sampling unrealistic conformations. To address this shortcoming, we present a method for performing constant pH molecular dynamics simulations (CpHMD) in explicit solvent using a d...
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Accurate and reliable pKa prediction is of significant interest, because it provides direct information of the protonation state of a protein and can be compared to experimental data. In this work pKa shifts of three aminoacids in proteins have been calculated using molecular dynamics free energy simulations with an explicit solvent and implicit Generalized Born solvent model. The direction of ...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2012
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2011.11.245