Computer-aided Design Methods Research Articles

SILCS-RNA: Toward a Structure-Based Drug Design Approach for Targeting RNAs with Small Molecules.

RNA molecules can act as potential drug targets in different diseases, as their dysregulated expression or misfolding can alter various cellular processes. Noncoding RNAs account for ∼70% of the human genome, and these molecules can have complex tertiary structures that present a great opportunity for targeting by small molecules. In the present study, the site identification by ligand competitive saturation (SILCS) computational approach is extended to target RNA, termed SILCS-RNA. Extensions to the method include an enhanced oscillating excess chemical potential protocol for the grand canonical Monte Carlo calculations and individual simulations of the neutral and charged solutes from which the SILCS functional group affinity maps (FragMaps) are calculated for subsequent binding site identification and docking calculations. The method is developed and evaluated against seven RNA targets and their reported small molecule ligands. SILCS-RNA provides a detailed characterization of the functional group affinity pattern in the small molecule binding sites, recapitulating the types of functional groups present in the ligands. The developed method is also shown to be useful for identification of new potential binding sites and identifying ligand moieties that contribute to binding, granular information that can facilitate ligand design. However, limitations in the method are evident including the ability to map the regions of binding sites occupied by ligand phosphate moieties and to fully account for the wide range of conformational heterogeneity in RNA associated with binding of different small molecules, emphasizing inherent challenges associated with applying computer-aided drug design methods to RNA. While limitations are present, the current study indicates how the SILCS-RNA approach may enhance drug discovery efforts targeting RNAs with small molecules.

In-silico Homology Modeling and Inhibitors Identification of Breast Cancer

Abstract: Azadirachta Indica (Neem) is the first introduced medicinal plant in ancient medicine system, used for various disease treatments and household remedies. Lots of phytochemicals have been isolated from the various parts of the tree to study their biological activities. Gedunin has shown anticancer activity and act as Heat shock protein 90 (Hsp90) inhibitor. Breast cancer one of the most common cancer which mainly develops from lobules or ducts. Triple-negative Breast Cancer (TNBC) is an aggressive type of breast cancer in which cancer cells does not have hormone receptors. Due to lack of hormone receptors many targeted therapies were developed for advance stage cancer. The interaction between drugs and protein were examined using spectroscopic techniques, to determine the drug stability and binding site of drug in protein. Computer-aided drug design method were used to develop and analyse the drugs. Interaction between protein and drugs visualize by using molecular graphic viewer tools, to identify protein conformation and binding energy of ligand and protein.

Application of Computer 3D Modeling Technology in Graphic Image Design.

In order to solve the problem that the manual input data work efficiency is low and the optimization cannot be achieved in the section modulus calculation, the author proposes a computer-aided 3D graphic design method for ship hull structure. First, complete the modeling of the ship hull, complete the statistical calculation of the size in the CAD platform, solve the static moment, and complete the three-dimensional modeling; Calculate the inertial load and wave load of the ship during work, and calculate the wave bending moment, and substitute it into the three-dimensional model for verification. Finally, according to the computer-aided three-dimensional graphic design process, the specification verification of the ship's scale is completed, the graphic file is associated with the database, and the three-dimensional graphic design is completed. Experimental results show that the maximum stress of the original three-dimensional integrated graphic design of the ship is 202 MPa, and the maximum deformation is 87.352 mm. Based on the computer-aided three-dimensional integrated graphic design of the ship, the maximum stress is 226 MPa, and the maximum deformation is 76.234 mm. In conclusion: the hull obtained by the computer-aided three-dimensional graphic design of the ship can effectively reduce the total area and materials of the midsection structure of the ship, reduce the weight of the hull, and realize the optimal configuration of the midsection material of the ship.

Allostery Inhibition of BACE1 by Psychotic and Meroterpenoid Drugs in Alzheimer's Disease Therapy.

In over a century since its discovery, Alzheimer’s disease (AD) has continued to be a global health concern due to its incurable nature and overwhelming increase among older people. In this paper, we give an overview of the efforts of researchers towards identifying potent BACE1 exosite-binding antibodies and allosteric inhibitors. Herein, we apply computer-aided drug design (CADD) methods to unravel the interactions of some proposed psychotic and meroterpenoid BACE1 allosteric site inhibitors. This study is aimed at validating the allosteric potentials of these selected compounds targeted at BACE1 inhibition. Molecular docking, molecular dynamic (MD) simulations, and post-MD analyses are carried out on these selected compounds, which have been experimentally proven to exhibit allosteric inhibition on BACE1. The SwissDock software enabled us to identify more than five druggable pockets on the BACE1 structural surface using docking. Besides the active site region, a melatonin derivative (compound 1) previously proposed as a BACE1 allostery inhibitor showed appreciable stability at eight different subsites on BACE1. Refinement with molecular dynamic (MD) simulations shows that the identified non-catalytic sites are potential allostery sites for compound 1. The allostery and binding mechanism of the selected potent inhibitors show that the smaller the molecule, the easier the attachment to several enzyme regions. This finding hereby establishes that most of these selected compounds failed to exhibit strong allosteric binding with BACE1 except for compound 1. We hereby suggest that further studies and additional identification/validation of other BACE1 allosteric compounds be done. Furthermore, this additional allosteric site investigation will help in reducing the associated challenges with designing BACE1 inhibitors while exploring the opportunities in the design of allosteric BACE1 inhibitors.

Two-piece magnet-retained shell manufactured by using milled and vat-polymerized methods for direct interim restorations

The shell technique has been described for fabricating direct interim restorations by using conventional and computer-aided design and computer-aided manufacturing (CAD-CAM) methods. However, the positioning of the shell over the tooth preparations can be challenging. In the present manuscript, the clinical and laboratory steps for manufacturing a 2-piece magnet-retained shell for direct interim restoration fabrication are described. The 2-piece shell was produced by combining milling and additive manufacturing procedures. The described technique aims to simplify the correct positioning of the shell and facilitate direct interim restoration fabrication.

Cover, Content, and Editorial Note from J Mol Docking Vol. 2 No. 1 June 2022

Assalamu’alaikum Wr. Wb.
 Alhamdulillahirabbil ‘alamin. After a long wait of almost 1 year from the first planned, finally, the new scientific journal of the Department of Pharmacy Universitas Muhammadiyah Palangkaraya can be published. This scientific journal was named Journal of Molecular Docking (J Mol Docking), inspired by one of the most popular in silico methods in computer-aided drug design. Journal of Molecular Docking is published every 6 months (2 issues/year) every June and December.
 This edition contains five articles consisting of writings from three countries, including India, Mexico, and Nigeria. The authors come from several institutions, including Maulana Azad National Urdu University, Osmania University, Osmania University College for Women, Vignan's Foundation for Science, Technology & Research, Ahmadu Bello University, Benemérita Universidad Autónoma de Puebla, Universidad Autónoma de Guerrero, The Tamil Nadu Dr. M.G.R. Medical University, and Anna University.
 Editorial boards are fully aware that this edition has room for improvement. Hence with all humility, willing to accept constructive suggestions and feedback for improvements to the publication for the next editions. The editorial board would like to thank all editors and reviewers, and contributors of the scientific articles who have provided the repertoire in this issue. We hope that all parties, especially the contributors of the articles, can re-participate for publication in the next edition on December 2022.
 Wassalamu’alaikum Wr. Wb.

Development of an Adaptive Centrifugal Working Tool for Mineral Fertilization Using Rapid Prototyping Technologies

Introduction. Improvement of the agro-industrial complex involves the creation of new and modernizations of existing working tools and machines. The important conditions for this are the application of modern technologies and ongoing cooperation with the actual manufacturing. The aim of the research is to develop an adaptive centrifugal working tool and improve the quality of mineral fertilization. Materials and Methods. The adaptive centrifugal working tool was developed and manufactured based on studying the state of the matter and requirements to machines for mineral fertilization. At all stages of the research, there were used computer-aided design and rapid prototyping methods based on additive technologies. Results. As a result of the use of the presented working tools, the machine operating width has increased by 10.0‒22.5%. Experimental working tools, in comparison with serial ones, allow decreasing uneven distribution of mineral fertilizers by 13.4% due to their redistribution from the central zone to the edges. Discussion and Conclusion. As a result of experimental studies, the efficiency of the developed adaptive centrifugal working tools has been proved. It allows increasing uniformity of mineral fertilizer distribution and the machine operating width. Modern design methods make it possible to considerably reduce time and costs.

Energy-efficient separation of propylene/propane by introducing a tailor-made ionic liquid solvent

In the petrochemical industry, the separation of propylene/propane is usually paid much attention due to its high energy-consuming and environmental challenges. In this work, an energy-efficient extractive distillation (ED) separation process of propylene/propane is proposed by introducing a tailor-made ionic liquid (IL) solvent. The structure optimization of ILs is performed with a novel design objective in the computer-aided ionic liquid design (CAILD) method. By solving a formulated CAILD-based mixed-integer nonlinear programming (MINLP) problem, the ethylimidazolium ethyl sulfate ([C2IM][EtSO4]) is identified as the best IL solvent. The separation performance of [C2IM][EtSO4] in the ED process of propylene/propane is then evaluated through rigorous process simulation in Aspen Plus. For comparison, the conventional separation process of propane/propylene is also simulated and optimized. Based on the optimized operations, in-depth energy and economic assessment are conducted for an industrial-scale separation of propane/propylene in a Chinese refining industry. Remarkably, the [C2IM][EtSO4]-based ED process has 68.9% energy savings and 74.7% cost reduction when compared to the conventional process.

A review of approaches in computer-aided drug design in drug discovery

The process of discovering and developing a new medication is often seen as a lengthy and expensive endeavors. As a result, computer-aided drug design methods are now frequently utilized to improve the efficiency of the drug discovery and development process. Various CADD approaches are regarded as potential techniques based on their needs; nevertheless, structure-based drug design and ligand-based drug design approaches are well-known as highly efficient and powerful strategies in drug discovery and development. Both of these approaches may be used in conjunction with molecular docking to conduct virtual screening for the purpose of identifying and optimizing leads. In recent years, computational tools have become increasingly popular in the pharmaceutical industry and academic fields as a means of improving the efficiency and effectiveness of the drug discovery and development pipeline. In this post, we'll go over computational methods, which are a creative way of discovering new leads and assisting in drug discovery and development research.

Application of Computer-Aided Precious Metal Materials in Electrochemistry of Ceramic Jewelry Design

In order to solve the electrochemical application of precious metal materials in ceramic jewelry design, a computer-aided design method of precious metal materials in ceramic jewelry was proposed. First, the potential energy surface analyzed in this paper is composed of the sum of disomy and trisomy, with different proportions of disomy and trisomy. Therefore, in the fitting process, the above two relations can be used to measure the contribution of the two-body term and the three-body term, respectively; secondly, from the viewpoint of lattice dynamics, precious metals are of special significance, because they are simple fcc lattice and large and pure single crystals can be obtained. Therefore, their accurate phonon dispersion curves can be obtained experimentally; finally, the phonon dispersion curves along the highly symmetric vector direction are given, and the calculated results are in good agreement with the experimental data. This shows that the new analytical potential energy surface accurately reproduces the interactions inside these crystals. The new analytical potential energy surfaces of the three noble metals correctly reproduce the macroscopic properties of the system, including elastic modulus, cohesive energy, and phonon dispersion curve, as well as important surface features. For all three systems, the order of the surface energies of the unreconstituted surfaces is (110) > (100) > (111), which is also correct. At the same time, the new potential energy surface gives the correct relaxation behavior of the unreconstituted surface.

Application of virtual reality technology in campus landscape roaming

With the popularity of the metaverse concept, virtual reality technology is widely used in people's lives, and the emergence of this new technology also brings new development opportunities to environmental design. Using computer-aided design, 3D roaming and other methods to build a virtual three-dimensional space, people can get an interactive and immersive experience. This paper takes the Liufang campus of Wuhan University of Technology as a prototype, and builds a 3D virtual campus landscape roaming based on SketchUp and Unity3D engine. It allows the campus to adapt to the development of digital informatization, and at the same time, through the roaming scene, the experiencer can understand the school style more intuitively and quickly, and help the campus culture to be better displayed.

Design Method of Circular Weft-Knitted Jacquard Fabric Based on Jacquard Module

Abstract Recently, there is an increasing interest in design of circular weft jacquard because of the pursuit of fashion and comfort. Aiming at the complexity of the computer-aided design method of the existing circular weft-knitted jacquard fabrics, which is not conducive to the rapid design and intelligible for designers, a design method was proposed to transform pattern notation into knitting diagram efficiently, which was based on knitting rules and its creation as a set of jacquard modules. Knitting characteristics of jacquard fabrics were studied as a precondition. On this basis, the design procedures of jacquard modules were analyzed and illustrated by taking tricolor bird's eye backing jacquard as an example. Jacquard modules with various jacquard effects were designed and stored in a jacquard module database. To mathematically describe pattern notation, knitting diagram, and jacquard module, two-dimensional matrixes were established by the method of mathematical modeling, and a corresponding algorithm for the transformation of the pattern to knitting information according to the knitting rules of jacquard modules, which can be applied to ordinary jacquard fabrics was summarized. The project of tricolor circular weft-knitted jacquard with bird's eye in the reverse and four-color air-layer jacquard were taken for instance to verify the models and algorithm. The results obtained show that the approach can efficiently and conveniently realize the designation and machine-knitting of weft-knitted jacquard fabric, which provide a theoretical basis and notation of modeling for the computer-aided design of circular weft-knitted jacquard fabrics.

A Computer-Aided Design-Based Tolerance Analysis of Assemblies With Form Defects and Deformations of Nonrigid Parts

Abstract Product assemblability and functional behavior are affected by geometric deviations. These deviations consist of manufacturing errors and part deformation defects caused by external loads. Taking the sources of deviations into account in tolerance analysis yields not only to more precise and reliable results but also to more complex tasks. In this context, the modeling of assembly parts with defects in a Digital MockUp (DMU) is quite promising. In this article, an integrated decision support tool is proposed to consider the causes of multiple defects, such as tolerances and external mechanical loads, in the tolerancing process. The worst-case concept and the small displacement torsor (SDT) are used to model rigid parts with orientation and positional defects. To model the part with form defects, random positions of each toleranced face points are determined using the Gaussian perturbation method (GPM) and considering the tolerance zone limits. A computer-aided design (CAD) method based on the B-spline interpolation allows the reconstruction of realistic surfaces of parts with form defects. Realistic configurations of nonrigid components subjected to external mechanical loads are determined using the finite element analysis (FEA). The realistic assembly configurations are performed by updating the mating constraints between planar and cylindrical parts. The proposed method considers all tolerance types on CAD models (positional, orientation, and form defects) and part deformations. The tolerance analysis is performed to check the compliance with the functional requirement (FR) and to correct the initial tolerance values. An industrial case study is used to validate the steps of the proposed tolerancing method.

In Silico Identification of Novel Quinoline-3-carboxamide Derivatives Targeting Platelet-Derived Growth Factor Receptor

Background: Several computer-aided drug design (CADD) methods enable the design and development of novel chemical entities. Structure-based drug design (SBDD) and the knowledge of in silico methods enable the visualization of the binding process of ligands to targets and to predict the key binding pocket sites and affinity of ligands to their target macromolecules. Objective: The present study was carried out to identify novel N-2-amino-N-phenyl quinoline-3- carboxamide (AQCMs) derivatives targeting Platelet-derived growth factor receptor (PDGFR) to cure cancer using in silico approach. Materials and Methods: AQCMs were designed using ChemAxon Marvin Sketch 5.11.5 software. SwissADME and admetSAR online webserver were used to predict physicochemical properties as well as the toxicity of compounds. Ligand-receptor interactions between quinoline-3-carboxamide derivatives with the target receptor (PDB: 5GRN) were carried out using molecular docking technique by employing various software like AutoDock 1.1.2, MGL Tools 1.5.6, Discovery Studio Visualizer v 20.1.0.19295, Procheck, ProtParam tool, and PyMOL. Results: In silico results reveal that all designed compounds had acceptable pharmacokinetic properties, were found to be orally bioavailable, and less harmful. Molecules from 36 to 39 showed better docking scores as compared to standard drugs sunitinib and tasquinimod. Conclusion: Increase in binding energy and the number of H-bonds established by AQCMs with below 3.40 Å distance interactions allows a valuable starting point in order to optimize compounds for further investigation. Pharmacokinetics and toxicological profile build up the applicability of quinoline-3-carboxamide moiety as a potential new candidate for the cure of cancer that could help the medicinal chemists for additional extensive in vitro, in vivo chemical, and pharmacological investigations.

Computer-aided efficient design and performance optimization of cutting head for roadheader

The cutting head is the core working mechanism of the roadheader for coal-rock materials cutting. The efficient and high performance design of cutting head is the key to improve the road head digging and mining technology. In this paper, based on cutting head design theory and virtual prototype technology, we propose a computer-aided structure design and performance optimization method for cutting head. We compile the calculation code and realize the reading and storing of relevant data through Excel. In particular, to obtain more realistic cutting performance data of the cutting head, we construct a coupling model of cutting head cutting rock wall based on virtual prototype technology, and then establish a database matching structural parameters, working parameters, coal-rock properties and cutting performance through extensive simulations. Based on the method, we complete the design of EBZ220 roadheader cutting head. We show that our method can realize the fast and efficient design of cutting head, and the designed cutting head has good working performance.

Computer-aided optimal design for flexible cable in aerospace products based on dynamic analogy modeling

Due to large, complex deformations, the accurate design of cables has become a major problem in the manufacturing of aerospace products. The current design method often leads to large products, uncertain centroids, and poor reliability. To solve these problems, a computer-aided optimal design method for flexible cables was proposed based on dynamic analogy modeling. A nonlinear optimization model was established by combining Cosserat theory and the minimum potential energy principle. The total deformation energy was considered as the optimization object, and Euler parameters were used as control variables to describe the cable geometric shape. Considering the length and bending radius requirements, the normalized form of the cable constraints was expressed by the cross-section position and orientation matrix. An efficient method to solve this problem using finite element discretization and the primitive dual interior point method was proposed. A digital wiring module was developed based on an open source geometry kernel system, and a cable geometry test bench was built. To verify our model, a satellite wiring simulation example was implemented using the module, SolidWorks, and the test bench. Our method achieved the optimal design for the cable length and geometric shape. A theoretical and technical foundation for effectively solving the problem of large cable manufacturing errors and realizing the lightweight design of aerospace products was outlined.

Research on Handicraft Design Based on Artificial Intelligence Technology in Complex Environments

In this twenty-first century, research is taking new dimension with the unpredictable development in information technology. With the aid of this technology, handicraft designs can be classified and made by utilizing artificial intelligence techniques. The Chinese handicraft designs will have unique style in the presentation. Using the artificial intelligence techniques, the arc styles of the handicraft design can be identified and classified. In complex environment like epidemic or pandemic situations, every user has to focus on the minor variations in financial aspects. Implementation of artificial intelligent technology will aid the user to get updated with the market strategy for financial allocation to resources. In the market, each arc style may have different demands and the charges will improve the profit for the company and also the country. In this study, the intelligent computer-aided art and craft design (ICAACD) method is implemented on the financial dataset of China and analysis is performed. This proposed system is compared with the existing algorithms such as GNNA, RNNA, and CNNA, and it is observed that the proposed ICAACD method outperforms with the accuracy of 82%.

Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Design and implementation of modular 6-degrees of freedom light-weight cooperative handling robot

Background: In view of the poor working environment and high labor intensity of manual loading and unloading in the production process of small forgings, a modular 6-DOF (degrees of freedom) light-weight cooperative handling robot is designed. Combined with the computer-aided design method, the modular and lightweight design is realized through the simulation of the actual motion situation. Methods: The overall configuration and modular joints of the robot were designed, and the static characteristics analysis of the whole robot and key parts was performed using Ansys to verify the rationality of the structural design. The kinematics model of the robot was established by using the Denavit-Hartenberg parameter method and the workspace of the robot was solved by forward kinematics simulation. Performance testing of the experimental prototype was executed. The repeated positioning accuracy was analyzed by a laser tracker to measure the position information at the end of the robot. Results: The results show that the repetitive positioning accuracy of the robot is 0.09mm, which can meet the requirements of loading and unloading handling in forging production. Conclusions: The study provides a theoretical basis for the structure design and optimization of the light-weight cooperative robot.

Design, Synthesis, and Biological Evaluation of Novel Psoralen-Based 1,3,4-Oxadiazoles as Potent Fungicide Candidates Targeting Pyruvate Kinase.

Pyruvate kinase (PK) has been considered as a promising fungicide target discovered in our previous studies. Natural compounds are important sources for discovery and development of new pesticides. To continue our ongoing studies on the discovery of novel PK-targeted fungicides, a series of novel psoralen derivatives including a 1,3,4-oxadiazole moiety were designed by a computer-aided pesticide molecular design method, synthesized, and evaluated for their fungicidal activity. The bioassay results indicated that compounds 11d, 11e, 11g, 11i, and 12a showed excellent in vitro fungicidal activity against Botrytis cinerea with EC50 values of 4.8, 3.3, 6.3, 5.4, and 3.9 μg/mL, respectively. They were more active than the corresponding positive control YZK-C22 [3-(4-methyl-1,2,3-thiadiazol-5-yl)-6-(trichloromethyl)-[1,2,4]-triazolo-[3,4-b][1,3,4]-thiadiazole] (with an EC50 value of 13.4 μg/mL). Compounds 11g and 11i displayed promising in vivo fungicidal activity against B. cinerea with 80 and 70% inhibition at a concentration of 200 μg/mL, respectively. They possessed much higher fungicidal activity than the positive control psoralen and comparable activity with the positive control pyrisoxazole. Enzymatic assays indicated that 11i showed good BcPK inhibition with an IC50 value of 39.6 μmol/L, comparable to the positive control YZK-C22 (32.4 μmol/L). Molecular docking provided a possible binding mode of 11i in the BcPK active site. Our studies suggested that the psoralen-based 1,3,4-oxadiazole 11i could be used as a new fungicidal lead targeting PK for further structural optimization.