TY - JOUR
T1 - In silico methods to assist drug developers in acetylcholinesterase inhibitor design
AU - Bermúdez-Lugo, J. A.
AU - Rosales-Hernández, M. C.
AU - Deeb, O.
AU - Trujillo-Ferrara, J.
AU - Correa-Basurto, J.
PY - 2011/3
Y1 - 2011/3
N2 - Alzheimer's disease (AD) is a neurodegenerative disease characterized by a low acetylcholine (ACh) concentration in the hippocampus and cortex. ACh is a neurotransmitter hydrolyzed by acetylcholinesterase (AChE). Therefore, it is not surprising that AChE inhibitors (AChEIs) have shown better results in the treatment of AD than any other strategy. To improve the effects of AD, many researchers have focused on designing and testing new AChEIs. One of the principal strategies has been the use of computational methods (structural bioinformatics or in silico methods). In this review, we summarize the in silico methods used to enhance the understanding of AChE, particularly at the binding site, to design new AChEIs. Several computational methods have been used, such as docking approaches, molecular dynamics studies, quantum mechanical studies, electronic properties, hindrance effects, partition coefficients (Log P) and molecular electrostatic potentials surfaces, among other physicochemical methods that exhibit quantitative structure-activity relationships.
AB - Alzheimer's disease (AD) is a neurodegenerative disease characterized by a low acetylcholine (ACh) concentration in the hippocampus and cortex. ACh is a neurotransmitter hydrolyzed by acetylcholinesterase (AChE). Therefore, it is not surprising that AChE inhibitors (AChEIs) have shown better results in the treatment of AD than any other strategy. To improve the effects of AD, many researchers have focused on designing and testing new AChEIs. One of the principal strategies has been the use of computational methods (structural bioinformatics or in silico methods). In this review, we summarize the in silico methods used to enhance the understanding of AChE, particularly at the binding site, to design new AChEIs. Several computational methods have been used, such as docking approaches, molecular dynamics studies, quantum mechanical studies, electronic properties, hindrance effects, partition coefficients (Log P) and molecular electrostatic potentials surfaces, among other physicochemical methods that exhibit quantitative structure-activity relationships.
KW - Acetylcholinesterase
KW - Docking
KW - In silico methods
KW - Molecular dynamics
KW - Sequence alignment
UR - http://www.scopus.com/inward/record.url?scp=79952779846&partnerID=8YFLogxK
U2 - 10.2174/092986711795029681
DO - 10.2174/092986711795029681
M3 - Artículo de revisión
SN - 0929-8673
VL - 18
SP - 1122
EP - 1136
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 8
ER -