Purdue University Graduate School
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Applications of Deep Neural Networks in Computer-Aided Drug Design

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posted on 2021-03-01, 23:10 authored by Ahmadreza Ghanbarpour GhouchaniAhmadreza Ghanbarpour Ghouchani
Deep neural networks (DNNs) have gained tremendous attention over the recent years due to their outstanding performance in solving many problems in different fields of science and technology. Currently, this field is of interest to many researchers and growing rapidly. The ability of DNNs to learn new concepts with minimal instructions facilitates applying current DNN-based methods to new problems. Here in this dissertation, three methods based on DNNs are discussed, tackling different problems in the field of computer-aided drug design.

The first method described addresses the problem of prediction of hydration properties from 3D structures of proteins without requiring molecular dynamics simulations. Water plays a major role in protein-ligand interactions and identifying (de)solvation contributions of water molecules can assist drug design. Two different model architectures are presented for the prediction the hydration information of proteins. The performance of the methods are compared with other conventional methods and experimental data. In addition, their applications in ligand optimization and pose prediction is shown.

The design of de novo molecules has always been of interest in the field of drug discovery. The second method describes a generative model that learns to derive features from protein sequences to design de novo compounds. We show how the model can be used to generate molecules similar to the known for the targets the model have not seen before and compare with benchmark generative models.

Finally, it is demonstrated how DNNs can learn to predict secondary structure propensity values derived from NMR ensembles. Secondary structure propensities are important in identifying flexible regions in proteins. Protein flexibility has a major role in drug-protein binding, and identifying such regions can assist in development of methods for ligand binding prediction. The prediction performance of the method is shown for several proteins with two or more known secondary structure conformations.


Degree Type

  • Doctor of Philosophy


  • Medicinal Chemistry and Molecular Pharmacology

Campus location

  • West Lafayette

Advisor/Supervisor/Committee Chair

Markus Lill

Additional Committee Member 2

Chiwook Park

Additional Committee Member 3

Daisuke Kihara

Additional Committee Member 4

Elizabeth Topp