Incorporating protein conformational flexibility into the calculation of pH-dependent protein properties.

Abstract:

:A method for combining calculations of residue pKa's with changes in the position of polar hydrogens has been developed. The Boltzmann distributions of proton positions in hydroxyls and neutral titratable residues are found in the same Monte Carlo sampling procedure that determines the amino acid ionization states at each pH. Electrostatic, Lennard-Jones potentials, and torsion angle energies are considered at each proton position. Many acidic and basic residues are found to have significant electrostatic interactions with either a water- or hydroxyl-containing side chain. Protonation state changes are coupled to reorientation of the neighboring hydroxyl dipoles, resulting in smaller free energy differences between neutral and ionized residues than when the protein is held rigid. Multiconformation pH titration gives better agreement with the experimental pKa's for triclinic hen egg lysozyme than conventional rigid protein calculations. The hydroxyl motion significantly increases the protein dielectric response, making it sensitive to the composition of the local protein structure. More than one conformer per residue is often found at a given pH, providing information about the distribution of low-energy lysozyme structures.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Alexov EG,Gunner MR

doi

10.1016/S0006-3495(97)78851-9

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

2075-93

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(97)78851-9

journal_volume

72

pub_type

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