Publication details

Calculating pKa of selected active site aminoacids in acetylcholinesterase

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WIESNER Jiří KOČA Jaroslav

Year of publication 2011
Type Appeared in Conference without Proceedings
MU Faculty or unit

Central European Institute of Technology

Description Acetylcholinesterase (AChE) is an important enzyme participating in nerve signal transmission connected with Alzheimer disease and nerve agent poisoning. Initial molecular dynamics simulations using the Amber force field 03 have revealed a strong dependence of the dynamics on the protonation state of the AChE's active site. Simulations of the protonated AChE were much more stable than that of the deprotonated form where significant changes in the vicinity of the charged residues occurred. AChE's active site contains three glutamic acid residues located close to each other (less than 8 A in the crystal structure). Using thermodynamic integration and the Amber force field 99SB, the pKa of these three glutamic acid residues was calculated. The calculated pKa shift values appear to be overestimated and differ for forward and backward runs significantly. According to the results, AChE should have two of the three glutamate residues protonated. This finding is in accord with the molecular dynamics simulation results.
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