Vol.:(0123456789) 1 3 Network Modeling Analysis in Health Informatics and Bioinformatics (2020) 9:54 https://doi.org/10.1007/s13721-020-00262-7 ORIGINAL ARTICLE In silico molecular studies of natural compounds as possible anti‑Alzheimer’s agents: ligand‑based design Opeyemi Iwaloye 1  · Olusola Olalekan Elekofehinti 1  · Abiola Ibrahim Momoh 1  · Kikiowo Babatomiwa 2  · Esther Opeyemi Ariyo 1 Received: 2 June 2020 / Revised: 20 July 2020 / Accepted: 27 July 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020 Abstract Alzheimer disease (AD) is the most common form of dementia contributing to about 60–70% of cases. β-Site amyloid pre- cursor protein cleaving enzyme-1 (BACE1) plays an important role in the onset of AD and has become one of the important drug targets for AD. This approach has led to the development of promising BACE1 inhibitors, many of which are going through diferent phases of clinical trials. Nonetheless, the high failure rate of lead drug candidates targeting BACE1 brought to the forefront the need for fnding new drugs to uncover the mystery behind AD. This study focused on virtual screening of ~ 33,000 natural compounds to fnd potential BACE1 inhibitors. Multiple ligands pharmacophore model was generated using PHASE to screen retrieved compounds against a four-site (ADDR) hypothesis. Molecular docking was performed to predict the binding status of the natural compounds. Based on binding afnity, the top eight compounds were chosen for further analysis. The docked complexes were analyzed for binding free energy using PRIME MM/GBA calculation. The compounds were fltered for drug-likeness using ADME/TOX (absorption, distribution, metabolism, excretion and toxicity) prediction. AutoQSAR (automated quantitative structure activity relationship) was used to build a model for the prediction of compounds bioactivities. Despite retrieving a large number of compounds with favorable binding afnity, only a few were selected to be promising based on their ADME/TOX proprieties, binding free energy and predicted pIC 50 . This study identifed four natural compounds (NPC469686, NPC262328, NPC29763 and NPC86744) as novel BACE1 inhibitors. The insights obtained from this study could be employed to produce next-generation drug for AD. Keywords BACE1 · Alzheimer disease · AutoQSAR · MMGBSA · Bioactivities 1 Introduction The word “dementia” describes a set of symptoms character- ized by progressive impairment and is also associated with impairment in functional abilities such as memory loss and difculties with thinking, problem-solving or language, and in many cases psychological symptoms (Ghosh and Osswald 2010; Foraker et al. 2015). About 10% of people develop this disorder at some point in their life (Loy et al. 2014). Alzheimer’s disease (AD), also known as Alzheimer’s, is the most common cause of dementia accounting for 60–70% of cases associated with dementia; other forms of demen- tia include vascular dementia, dementia with Lewy bodies, and a group of diseases that contribute to frontotemporal dementia (Burns and Ilife 2009). AD is a disease of neuro- degeneration which usually worsen as it progresses and may ultimately lead to death (Todd et al. 2013). The disease pro- cess is associated with plaques and neurofbrillary tangles * Opeyemi Iwaloye popenapoleon@gmail.com Olusola Olalekan Elekofehinti Sola_eleko@yahoo.com Abiola Ibrahim Momoh momohcares11@gmail.com Kikiowo Babatomiwa mactomiwa@gmail.com Esther Opeyemi Ariyo estherariyo87@gmail.com 1 Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State, Nigeria 2 Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria