Advances in De Novo Drug Design : From Conventional to Machine Learning Methods

De novo drug design is a computational approach that generates novel molecular structures from atomic building blocks with no a priori relationships. Conventional methods include structure-based and ligand-based design, which depend on the properties of the active site of a biological target or its known active binders, respectively. Artificial intelligence, including ma-chine learning, is an emerging field that has positively impacted the drug discovery process. Deep reinforcement learning is a subdivision of machine learning that combines artificial neural networks with reinforcement-learning architectures. This method has successfully been em-ployed to develop novel de novo drug design approaches using a variety of artificial networks including recurrent neural networks, convolutional neural networks, generative adversarial networks, and autoencoders. This review article summarizes advances in de novo drug design, from conventional growth algorithms to advanced machine-learning methodologies and high-lights hot topics for further development.Peer reviewe

Evaluation of SAR for Amphotericin B Derivatives by Artificial Neural Network

Purpose: This study was designed to investigate the role of several descriptive structure-activity features in the antifungal drug, amphotericin B and analyze them by artificial neural networks. Method: Artificial neural networks (ANN) based on the back-propagation algorithm were applied to a structure-activity relationship (SAR) study for 17 amphotericin B derivatives with antifungal and membrane directed activity. A series of modified ANN architectures was made and the best result provided the ANN model for prediction of antifungal activity using the structural and biologic property descriptors. Results: The best architecture, in terms of cycles of calculation was 12-15-2. Among the most important factors were biological descriptors that correlated best with the model produced by ANN. Among the chemical and structural descriptors, positive charge on Y substitution was found to be the most important, followed by lack of availability of free carboxyl and parachor. Conclusion: This model is found to be useful to elucidate the structural requirements for the antifungal activity and can be applied in the design and activity prediction of the new amphotericin B derivatives. Keywords: Amphotericin B, SAR, Artificial Neural Network. > Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 517-52

AI and OR in management of operations: history and trends

The last decade has seen a considerable growth in the use of Artificial Intelligence (AI) for operations management with the aim of finding solutions to problems that are increasing in complexity and scale. This paper begins by setting the context for the survey through a historical perspective of OR and AI. An extensive survey of applications of AI techniques for operations management, covering a total of over 1200 papers published from 1995 to 2004 is then presented. The survey utilizes Elsevier's ScienceDirect database as a source. Hence, the survey may not cover all the relevant journals but includes a sufficiently wide range of publications to make it representative of the research in the field. The papers are categorized into four areas of operations management: (a) design, (b) scheduling, (c) process planning and control and (d) quality, maintenance and fault diagnosis. Each of the four areas is categorized in terms of the AI techniques used: genetic algorithms, case-based reasoning, knowledge-based systems, fuzzy logic and hybrid techniques. The trends over the last decade are identified, discussed with respect to expected trends and directions for future work suggested

Automated identification of Fos expression

The concentration of Fos, a protein encoded by the immediate-early gene c-fos, provides a measure of synaptic activity that may not parallel the electrical activity of neurons. Such a measure is important for the difficult problem of identifying dynamic properties of neuronal circuitries activated by a variety of stimuli and behaviours. We employ two-stage statistical pattern recognition to identify cellular nuclei that express Fos in two-dimensional sections of rat forebrain after administration of antipsychotic drugs. In stage one, we distinguish dark-stained candidate nuclei from image background by a thresholding algorithm and record size and shape measurements of these objects. In stage two, we compare performance of linear and quadratic discriminants, nearest-neighbour and artificial neural network classifiers that employ functions of these measurements to label candidate objects as either Fos nuclei, two touching Fos nuclei or irrelevant background material. New images of neighbouring brain tissue serve as test sets to assess generalizability of the best derived classification rule, as determined by lowest cross-validation misclassification rate. Three experts, two internal and one external, compare manual and automated results for accuracy assessment. Analyses of a subset of images on two separate occasions provide quantitative measures of inter- and intra-expert consistency. We conclude that our automated procedure yields results that compare favourably with those of the experts and thus has potential to remove much of the tedium, subjectivity and irreproducibility of current Fos identification methods in digital microscopy

A Neurogenetic Algorithm Based on Rational Agents

Lately, a lot of research has been conducted on the automatic design of artificial neural networks (ADANNs) using evolutionary algorithms, in the so-called neuro-evolutive algorithms (NEAs). Many of the presented proposals are not biologically inspired and are not able to generate modular, hierarchical and recurrent neural structures, such as those often found in living beings capable of solving intricate survival problems. Bearing in mind the idea that a nervous system's design and organization is a constructive process carried out by genetic information encoded in DNA, this paper proposes a biologically inspired NEA that evolves ANNs using these ideas as computational design techniques. In order to do this, we propose a Lindenmayer System with memory that implements the principles of organization, modularity, repetition (multiple use of the same sub-structure), hierarchy (recursive composition of sub-structures), minimizing the scalability problem of other methods. In our method, the basic neural codification is integrated to a genetic algorithm (GA) that implements the constructive approach found in the evolutionary process, making it closest to biological processes. Thus, the proposed method is a decision-making (DM) process, the fitness function of the NEA rewards economical artificial neural networks (ANNs) that are easily implemented. In other words, the penalty approach implemented through the fitness function automatically rewards the economical ANNs with stronger generalization and extrapolation capacities. Our method was initially tested on a simple, but non-trivial, XOR problem. We also submit our method to two other problems of increasing complexity: time series prediction that represents consumer price index and prediction of the effect of a new drug on breast cancer. In most cases, our NEA outperformed the other methods, delivering the most accurate classification. These superior results are attributed to the improved effectiveness and efficiency of NEA in the decision-making process. The result is an optimized neural network architecture for solving classification problems

Learning Multimodal Graph-to-Graph Translation for Molecular Optimization

We view molecular optimization as a graph-to-graph translation problem. The goal is to learn to map from one molecular graph to another with better properties based on an available corpus of paired molecules. Since molecules can be optimized in different ways, there are multiple viable translations for each input graph. A key challenge is therefore to model diverse translation outputs. Our primary contributions include a junction tree encoder-decoder for learning diverse graph translations along with a novel adversarial training method for aligning distributions of molecules. Diverse output distributions in our model are explicitly realized by low-dimensional latent vectors that modulate the translation process. We evaluate our model on multiple molecular optimization tasks and show that our model outperforms previous state-of-the-art baselines