File Name: molecular design concepts and applications .zip
A new field of organic materials science that deals with amorphous molecular glasses has been opened up. In addition, amorphous molecular materials have constituted a new class of functional organic materials for use in various applications.
- Molecular engineering
- Molecular Design: Concepts and Applications
- Molecular design . Concepts and applications
- BRADSHAW: a system for automated molecular design
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Here, we show an autonomous search system for organic molecules implemented by a reinforcement learning algorithm, and apply it to molecular dynamics simulations of viscosity. The evaluation is dramatically accelerated by three orders of magnitude using a femto-second stress-tensor correlation, which underlies the glass-transition model. We experimentally examine one of 55, lubricant oil molecules found by the system. This study indicates that merging simulations and physical models can open a path for simulation-driven approaches to materials informatics.
The development of materials conventionally depends on human sense and trial-and-error synthesis. Such laborious developments are expected to be accelerated by materials informatics MI 1 , 2 , which is commonly implemented by virtual screening see Fig. After training on existing data, a machine-learning model predicts the target properties of materials based on the features of known materials 3 , 4 , 5 , 6 , 7 , 8 , 9.
Rapid inference by machine learning extracts the potential candidates from hundreds of thousands of compounds in a material database. This subset of the candidates is then examined experimentally. However, the prediction ability is effective only when the target materials are within an interpolation space coordinated by a supervised dataset.
To discover truly new materials, we should explore outside the scope of known materials. An autonomous search scheme beyond the interpolation space is called a closed-loop search 1.
The system configuration is illustrated in Fig. Here, a machine-learning search model accompanies robotics or simulation software. The search model receives feedback from the evaluated properties, and decides the material proposals in the next loop. This search-evaluation loop iterates until the material structure is optimized with respect to a target property.
Search algorithms for this purpose are numerous and varied 10 , 11 , 12 , 13 , An example is the artificial neural network in the chemical language SMILES, which generates a continuous latent space of molecules, and seeks the high-scoring molecules by a gradient-based optimization procedure 10 , Elsewhere, prospective molecular structures were generated by a Bayesian approach using forward and backward predictions in the structure—property relationship To design synthetic strategies and uncover new organic materials, Yang et al.
Its aim is to maximize the prospective reward of molecules 13 , However, no matter what search algorithms are used, a long evaluation time is a major bottleneck in the loop. Ab initio calculations provide important material properties such as formation energies and band gaps. These static properties can be obtained at reasonable computation cost only by advanced algorithms and multicore architectures 18 , 19 , 20 , Transport-related properties, such as ion conductivity and viscosity, must be assessed in molecular dynamics MD calculations, which simulate the atomic dynamics of molecules.
Although the evaluated transport properties are based on statistical physics, MD calculations cannot be a high-throughput evaluator 22 , because reliable ensemble averaging requires a huge number of MD steps 23 , Another important consideration is accuracy of the empirical force fields. This topic has been actively studied in recent years, with developments of machine-learning potentials trained on appropriate ab initio reference data 25 , 26 , 27 , 28 , As an example of transport properties, we focus on viscosity because viscosity is related to tribological properties 30 , 31 and its reciprocal value represents a diffusion coefficient.
These properties are fundamental in mechanical and chemical engineering, which use oil and electrolytes on a daily basis. Our system performs ultra-fast MD evaluations that alleviate the time-demanding bottleneck of autonomous systems. We first explain the conventional and proposed fast viscosity evaluations by MD simulations, define the target property, and explain the rules of oil-molecule generation in MCTS. After the closed-loop search, the MI-designed oil molecule is synthesized and its viscosity performance is experimentally examined.
Finally, we inductively analyze the obtained large data to guide the development of lubricants. The technical details are provided in the Methods section and Supplementary Notes. One conventional schemes for obtaining transport properties is the Green—Kubo GK formalism 32 , Non-diagonal elements of a stress tensor P ij is observed in a MD simulation of liquid molecules. The red lines are the averaged values over the samplings. After a long t , the variations among the samplings of the correlation are enlarged, meaning that the long-future state is loosely associated with its present state.
As evidenced in Eq. Based on this insight, we suggest that if the viscosity can be predicted through the short-time correlation, the number of sampling MD steps can be reduced in the viscosity evaluation. Such a strategy is sought in this paper. To realize the above idea, we import an elastic concept of liquid viscosity called the shoving model 34 , 35 , This model describes liquid from an atomic viewpoint as shown in Fig.
In the liquid state, a component molecule is surrounded by other liquid molecules in a caged space. Driven by thermal fluctuations, each molecule repeatedly collides with its neighbors. After a certain relaxation time, a molecule escapes from the cage by pushing its neighbors away.
Through iterations of this local relaxation, all molecules are eventually rearranged and the liquid flows macroscopically. This phenomenological viewpoint suggests that the structural relaxation related to viscosity can be well represented by the energy required to push the surrounding molecules.
The energy barrier is then proportional to the shear modulus of the liquid. Combined with transition-state theory 37 , the shoving model provides an Arrhenius-type equation of viscosity as. Equation 2 demonstrates that viscosity is correlated with the stiffness of the liquid, which is measured under a given instantaneous force. The shoving model was originally developed to clarify the atomic mechanism of glass transition.
Here, we employ it to accelerate the MD evaluation of viscosity, as described below. Note that as Eq. To improve the accuracy of our evaluation, we modify the original Arrhenius equation in Eq. Commonly used in lubrication engineering, this model corrects the viscosity—temperature relation with respect to the boiling point of the liquid 38 , Combining the van Velzen model with Eqs. Fitting Eq. This value is consistent with the fitted value.
Note that the accuracy of the proposed approach may degrade in small-molecule cases. As a target property for optimization, viscosity alone is unsuitably trivial. Viscosity typically increases with number of constituent atoms of a lubricant molecule, because longer molecules become more entangled in the liquid state than short molecules Instead, we target the viscosity index VI , which indicates the temperature sensitivity of viscosity Machinery equipment requires high-VI oil for stable mechanical operations in various environments.
The reference viscosities can be obtained from a viscosity conversion table 42 , To resolve these problems, the DVI was proposed as. Tribological properties such as oil film thickness and viscosity resistance at the sliding interface depend more on viscosity than the kinematic viscosity.
The remaining component of the autonomous design system is a search algorithm that generates molecular structures with the optimal target properties. The search algorithm should comprise both an efficient search strategy in regarding to inherent molecular representations and generation rules to meet material requirements. This study employs the MCTS as the search algorithm, which describes a molecule by a graph structure. Oil molecules synthesized and purified from crude oil generally have hydrocarbon chain structures with several branches.
To represent such structures, we defined different types of molecular fragments for the main and side chains of the molecules as follows:. The initial molecular fragment, called a root node, is C. We then restricted the generated molecules to lubricants.
Unbranched molecules are inappropriate because they have high freezing points, so are prone to waxing at the operating temperature. To generate molecules with one or more branches, we rejected the no-branch molecules during the rollout operation of MCTS.
The branched molecules were then restricted to the allowable viscosity range. An excessively high viscosity increases the fuel consumption, whereas a very low viscosity leads to scuffing. The preferred kinematic viscosity of the base oil of automobile lubricants ranges from 3.
As viscosity is proportional to the number of constituent atoms 39 , a typical oil molecule should contain 20—40 carbons In summary, we define three search rules: define the molecular fragments, prohibit the unbranched molecules, and impose the ending condition. The closed-loop feasibility is mainly determined by the acceleration extent of the MD evaluations. As a baseline method, we employed the conventional Einstein—Helfand EH scheme 33 , which evaluates the viscosity by the mean-squared displacement of P xy.
We emphasize that this baseline was selected for a convenient comparison, because the EH scheme is defined to avoid erroneous negative viscosity, unlike the GK scheme. The computational details are provided in the Methods section. Under the same sampling conditions, the root-mean-squared error RMSE was 3. In the present method, the STD is only 3. We roughly estimated that to attain the same statistical accuracy as the EH method, the fast evaluation reduced the number of samplings in the MD steps to approximately 3.
The fast evaluation is examined in detail in Supplementary Note 3. The red circles are averaged over the MD trajectories. The reference organic molecules and MD conditions are described in the Methods section.
Molecular Design: Concepts and Applications
Molecular engineering is an emerging field of study concerned with the design and testing of molecular properties, behavior and interactions in order to assemble better materials, systems, and processes for specific functions. Molecular engineering is highly interdisciplinary by nature, encompassing aspects of chemical engineering , materials science , bioengineering , electrical engineering , physics , mechanical engineering , and chemistry. There is also considerable overlap with nanotechnology , in that both are concerned with the behavior of materials on the scale of nanometers or smaller. Given the highly fundamental nature of molecular interactions, there are a plethora of potential application areas, limited perhaps only by one's imagination and the laws of physics. However, some of the early successes of molecular engineering have come in the fields of immunotherapy, synthetic biology, and printable electronics see molecular engineering applications.
MOLECULAR DESIGN. CONCEPTS AND APPLICATIONS. John Wiley & Sons. ISBN ISBN Paperback. pages.
Molecular design . Concepts and applications
Life science in general and chemistry in particular are inaccessible to blind and visually impaired BVI students at the exception of very few individ-uals who have overcome, in a seemingly miraculous way, the hurdles that pave the way to higher education and professional competency. AsteriX-BVI a publicly accessible web server, developed at the Radboud University in the Netherlands already allows BVI scientists to perform a complete series of tasks to automatically manage results of quantum chemical calculations and produce a 3D representation of the optimized structures into a 3D printable, haptic-enhanced format that includes Braille annotations. We report here the implementation of Molecular Fabricator 1. This molecular editor allows BVI scientists to conceptualize complex organic molecules in their mind and subsequently create them via the server.
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BRADSHAW: a system for automated molecular design
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. Corpus ID: Molecular design. Schneider , Karl-Heinz Baringhaus Published This book focuses on how different concepts and molecular modeling strategies could be exploited to design the molecular architecture of ligands for specific targets, as new drug candidates. The authors have large experience in drug discovery, occupying head positions in European pharmaceutical industries, which was crucial to their particular form to address the main design-related medicinal chemistry topics along the five chapters of the book.
This paper introduces BRADSHAW B iological R esponse A nalysis and D esign S ystem using an H eterogenous, A utomated W orkflow , a system for automated molecular design which integrates methods for chemical structure generation, experimental design, active learning and cheminformatics tools. The simple user interface is designed to facilitate access to large scale automated design whilst minimising software development required to introduce new algorithms, a critical requirement in what is a very fast moving field. The system embodies a philosophy of automation, best practice, experimental design and the use of both traditional cheminformatics and modern machine learning algorithms. The search for efficient and effective drug design strategies has been a constant feature of the scientific literature since the concept of rational discovery was introduced by Elion and Hitchings [ 1 , 2 , 3 ]. The field of quantitative structure—activity relationship QSAR analysis [ 4 , 5 , 6 ] developed alongside the rational approach, with the goal of being able to use chemical structures and biological response to develop hypotheses, predictions and design experiments which would provide an efficient path to optimise chemical series into promising drug candidates.
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