TY - JOUR
T1 - Molecular dynamics of mouse acetylcholinesterase complexed with huperzine A
AU - Tara, Sylvia
AU - Helms, Volkhard
AU - Straatsma, T. P.
AU - McCammon, J. Andrew
PY - 1999/10/5
Y1 - 1999/10/5
N2 - Two molecular dynamics simulations were performed for a modeled complex of mouse acetylcholinesterase liganded with huperzine A (HupA). Analysis of these simulations shows that HupA shifts in the active site toward Tyr 337 and Phe 338, and that several residues in the active site area reach out to make hydrogen bonds with the inhibitor. Rapid fluctuations of the gorge width are observed, ranging from widths that allow substrate access to the active site, to pinched structures that do not allow access of molecules as small as water. Additional openings or channels to the active site are found. One opening is formed in the side wall of the active site gorge by residues Val 73, Asp 74, Thr 83, Glu 84, and Asn 87. Another opening is formed at the base of the gorge by residues Trp 86, Val 132, Glu 202, Gly 448, and Ile 451. Both of these openings have been observed separately in the Torpedo californica form of the enzyme. These channels could allow transport of waters and ions to and from the bulk solution.
AB - Two molecular dynamics simulations were performed for a modeled complex of mouse acetylcholinesterase liganded with huperzine A (HupA). Analysis of these simulations shows that HupA shifts in the active site toward Tyr 337 and Phe 338, and that several residues in the active site area reach out to make hydrogen bonds with the inhibitor. Rapid fluctuations of the gorge width are observed, ranging from widths that allow substrate access to the active site, to pinched structures that do not allow access of molecules as small as water. Additional openings or channels to the active site are found. One opening is formed in the side wall of the active site gorge by residues Val 73, Asp 74, Thr 83, Glu 84, and Asn 87. Another opening is formed at the base of the gorge by residues Trp 86, Val 132, Glu 202, Gly 448, and Ile 451. Both of these openings have been observed separately in the Torpedo californica form of the enzyme. These channels could allow transport of waters and ions to and from the bulk solution.
KW - Acetylcholinesterase
KW - Active site gorge
KW - Backdoor
KW - Gating
KW - Huperzine A
KW - Molecular dynamics simulations
KW - Side channel
UR - http://www.scopus.com/inward/record.url?scp=0033527325&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0282(19991005)50:4<347::AID-BIP1>3.0.CO;2-R
DO - 10.1002/(SICI)1097-0282(19991005)50:4<347::AID-BIP1>3.0.CO;2-R
M3 - Article
C2 - 10423544
AN - SCOPUS:0033527325
SN - 0006-3525
VL - 50
SP - 347
EP - 359
JO - Biopolymers
JF - Biopolymers
IS - 4
ER -