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Full-Text Articles in Chemicals and Drugs

Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study Of Plasmodium Falciparum Hsp70s, Arnold Amusengeri, Lindy Astl, Kevin Lobb, Gennady M. Verkhivker, Özlem Tastan Bishop Nov 2019

Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study Of Plasmodium Falciparum Hsp70s, Arnold Amusengeri, Lindy Astl, Kevin Lobb, Gennady M. Verkhivker, Özlem Tastan Bishop

Mathematics, Physics, and Computer Science Faculty Articles and Research

Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malaria cases. To prevent catastrophic results, we need to find non-conventional approaches. Allosteric drug targeting sites and modulators might be a new hope for malarial treatments. Heat shock proteins (HSPs) are potential malarial drug targets and have complex allosteric control mechanisms. Yet, studies on designing allosteric modulators against them are limited. Here, we identified allosteric …


Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker Jun 2019

Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to …


Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao Feb 2019

Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an …