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Molecular dynamics simulations of human carbonic anhydrase II: Insight into experimental results and the role of solvation
Author(s) -
Lu Dongsheng,
Voth Gregory A.
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19981001)33:1<119::aid-prot11>3.0.co;2-o
Subject(s) - chemistry , solvation , carbonic anhydrase ii , protonation , molecular dynamics , molecule , active site , carbonic anhydrase , crystallography , bound water , computational chemistry , catalysis , enzyme , ion , organic chemistry
Abstract In this paper, the carbonic anhydrase II (CA II) enzyme active site is modeled using ab initio calculations and molecular dynamics simulations to examine a number of important issues for the enzyme function. It is found that the Zn 2+ ion is dominantly tetrahedrally coordinated, which agrees with X‐ray crystallographic studies. However, a transient five‐fold coordination with an extra water molecule is also found. Studies of His64 conformations upon a change in the protonation states of the Zn‐bound water and the His64 residue also confirm the results of an X‐ray study which suggest that the His64 conformation is quite flexible. However, the degree of water solvation is found to affect this behavior. Water bridge formation between the Zn‐bound water and the His64 residue was found to involve a free energy barrier of 2–3 kcal/mol and an average lifetime of several picoseconds, which supports the concept of a proton transfer mechanism through such a bridge. Mutations of various residues around the active site provide further insight into the corresponding experimental results and, in fact, suggest an important role for the solvent water molecules in the CA II catalytic mechanism. Proteins 33:119–134, 1998. © 1998 Wiley‐Liss, Inc.