Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates for liposomal remote loading

Pectin is a complex polysaccharide found in the cell walls of plants and consisting mainly of esterified D-galacturonic acid resides in α-(1-4) chain. In production of fruit juice, pectin contributes to fruit juice viscosity, thereby reducing the juice production and increasing the filtration time. Polygalacturonase improves the juice production process by rapid degradation of pectin. In this project we have designed a novel polygalacturonase enzyme using computer aided design approaches. The three dimension structure of polygalacturonase is first modeled on the basis of the known crystal structure. The active site in this enzyme is identified by manual and automated docking methods. Lamarckian genetic algorithm is used for automated docking and the active site is validated by comparing with existing experimental data. This is followed by in silico mutations of the enzymes and the automated docking process is repeated using the mutant enzymes. The strength of the binding of the ligands inside the active site is evaluated by computing the binding score using Potential Mean Force (PMF) method. The in silico mutations R256Q and K258N are found to decrease the binding strength of the ligand at the active site, indicating lowering of enzyme activity, which is consistent with the experimental results. Hence in silico mutations can be used to design new polygalacturonase enzymes with improved enzyme activity.ABSTRAK: Pektin adalah polisakarida kompleks yang terdapat di dalam dinding sel tumbuhan dan sebahagian besarnya terdiri daripada asid D-galakturonik terester yang ditemui di dalam rantaian α-(1-4). Dalam penghasilan jus buah-buahan, pektin menyumbang dalam kepekatan jus buah-buahan, di mana ia mengurangkan penghasilan jus dan menambahkan masa penapisan. Poligalakturonase meningkatkan proses penghasilan jus dengan pemecahan pektin dengan cepat. Dalam projek ini, kami telah merangka satu enzim poligalakturonase baru dengan menggunakan pendekatan reka bentuk berbantukan komputer. Struktur tiga dimensi poligalakturonase ini pada permulaannya dimodelkan berasaskan kepada struktur kristal. Tapak aktif enzim ini dikenali pasti dengan kaedah mengedok manual dan automatik. Algoritma genetik Lamarckian digunakan untuk dok berautomatik dan tapak aktif ini disahkan dengan perbandingan dengan data eksperimental yang sedia ada. Kaedah ini diikuti pula dengan mutasi in siliko enzim dan proses mengedok automatik diulangi dengan menggunakan enzim mutan. Kekuatan ikatan ligan yang berada di dalam tapak aktif dinilai dengan mengira kiraan ikatan menggunakan kaedah Min Keupayaan Daya (Potential Mean Force (PMF)). Mutasi in siliko R256Q dan K258N merupakan penyebabpenurunan dalam kekuatan ikatan ligan di tapak aktif, menunjukkan pengurangan dalam aktiviti enzim, di mana ianya konsisten dengan keputusan ekperimental. Jesteru, mutasi siliko boleh digunakan untuk mereka enzim poligalakturonase baru dengan mempertingkatkan aktiviti enzim.

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Computer-Aided Design of Protective Structures: Numerical Simulations and Experimental Validation

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.82.686 ◽

2011 ◽

Vol 82 ◽

pp. 686-691 ◽

Cited By ~ 4

Author(s):

Sumita Dey ◽

Tore Børvik ◽

Odd Sture Hopperstad

Keyword(s):

Finite Element ◽

Computer Aided Design ◽

Experimental Validation ◽

Plate Thickness ◽

Experimental Tests ◽

Layered Plates ◽

Explicit Finite Element ◽

Ballistic Protection ◽

Computer Aided ◽

Aided Design

This paper aims through several numerical studies to highlight some effects of layering plates in ballistic protection. The possible increase in perforation resistance by varying the material properties of the plates, the individual plate thickness (the total plate thickness is constant) and the stacking of individual plates in a double-layered target when struck by blunt and ogival nose projectiles has been investigated. This was done by conducting non-linear finite element simulations of the perforation process using an experimentally validated numerical model and an explicit finite element code. These studies are difficult to carry out experimentally due to the many materials and thicknesses involved and computer-aided design is thus an attractive approach. The numerical design indicates that it is possible to considerably increase the overall ballistic protection level by using double-layered plates and a proper design. Some of the most promising designs were then selected for experimental validation. The experimental tests gave completely opposite results than the computer-aided design, and the reasons for this will be discussed in some detail.

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Experimental Validation of the Computer Aided Design Technique for Seat Comfort Design and Evaluation

10.4271/2013-01-0448 ◽

2013 ◽

Author(s):

Saed T. Amer ◽

Landon Onyebueke

Keyword(s):

Computer Aided Design ◽

Experimental Validation ◽

Design Technique ◽

Seat Comfort ◽

Computer Aided ◽

Aided Design

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Pemanfaatan bioinformatika dalam bidang pertanian dan kesehatan (The utilization of bioinformatics in the field of agriculture and health)

E-Journal Menara Perkebunan ◽

10.22302/iribb.jur.mp.v85i2.237 ◽

2017 ◽

Vol 85 (2) ◽

Author(s):

Arli Aditya PARIKESIT ◽

Dito ANUROGO ◽

Riza A PUTRANTO

Keyword(s):

Gene Expression ◽

Drug Design ◽

Expression Analysis ◽

In Silico ◽

Computer Aided Design ◽

Gene Expression Analysis ◽

Genetic Maps ◽

In Silico Drug Design ◽

Computer Aided ◽

Aided Design

Bioinformatics can be used to manage the data storage resulted from in silico molecular biology experiments. Off-network (offline) applications require large computing resources, in which researchers in the bioinformatics field of agriculture and health sectors do not necessarily possess. This review paper addressed examples of affordable and applicable in silico analytical cases in both mentioned sectors. Genome sequence analysis and in silico drug design using (1) a computational method, pharmacokinetic parameter prediction, (2) Computer Aided Design and Drafting (CADD) technology, (3) potential protein action prediction, (4) OMICs application in stem cell biology, and (5) lncRNAs based database computing internet sites is one of examples. In agriculture, bioinformatics-based research has been used in (1) the development of molecular markers; (2) the design of primer for differential gene expression analysis; (3) the development of genetic maps; and (4) gene expression analysis. Further application of bioinformatics also targets the design of applicative products for pest control and the protection of plant varieties in the farm. Through this example, novice researchers in the bioinformatics field of agriculture and health sectors can conduct sophisticated research using standard computer tools, internet networks, and sufficient knowledge about bioinformatics. On the other hand, multidisciplinary collaboration between these scientists can be carried out through social networking. The synergy can be directed to improve computing capabilities and data analysis via procurement of computing resources and use of public information clusters. [Key words: genome sequences, in silico drug design, online, bioinformatics, health, agriculture.] AbstrakBioinformatika dapat digunakan dalam manajemen informasi di bidang penyimpanan data in silico dari eksperimen biologi molekuler. Aplikasi luar jaringan (luring) memerlukan sumber daya komputasi yang besar, yang belum tentu dimiliki oleh para peneliti dalam bidang bioinformatika kesehatan dan pertanian. Kajian ilmiah ini membahas contoh kasus analisis in silico yang terjangkau dan aplikatif dalam bidang kesehatan dan pertanian. Contoh kasus tersebut adalah analisis sekuen genom dan desain obat in silico, menggunakan pendekatan metode komputasional, prediksi parameter farmakokinetik, teknologi Computer Aided Design and Drafting (CADD), prediksi potensial aksi protein, aplikasi OMICs pada biologi sel punca, hingga komputasi basis data lncRNAs berbasis situs internet. Pada bidang pertanian, penelitian berbasis bioinformatika telah digunakan dalam (1) pengembangan penanda molekuler; (2) desain primer untuk analisis ekspresi gen diferensial; (3) pengembangan peta genetik; dan (4) analisis ekspresi gen. Pemanfaatan bio-informatika dalam ilmu terapan dibidang pertanian juga menyasar desain produk aplikatif untuk pengendalian hama dan perlindungan varietas tanaman. Melalui contoh tersebut, peneliti pemula dibidang bioinformatika kesehatan dan pertanian dapat melakukan penelitian canggih hanya dengan alat komputer standar, jaringan internet, dan pengetahuan mencukupi tentang bioinformatika. Disisi lain, sinergi dan kolaborasi antar peneliti multi-displiner dapat dilakukan melalui penggunaan jejaring sosial. Sinergi tersebut dapat diarahkan untuk meningkatkan kemampuan komputasi dan analisis data melalui pengadaan sumber daya komputasi dan penggunaan klaster informatika publik.[Kata kunci: sekuen genom, desain obat in silico, daring, bioinformatika, kesehatan, pertanian]

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Computer-Aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates

10.1201/9781351018302 ◽

2019 ◽

Author(s):

Satya eswari Jujjavarapu ◽

Swasti Dhagat ◽

Manisha Yadav

Keyword(s):

Computer Aided Design ◽

Drug Candidates ◽

Computer Aided ◽

Antimicrobial Lipopeptides ◽

Aided Design

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Computer-Aided Design of Coumarins for Neurodegenerative diseases: Trends of the Last Decade

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666211011101429 ◽

2021 ◽

Vol 21 ◽

Author(s):

Estela Guardado Yordi ◽

Lourdes Santana ◽

Eugenio Uriarte ◽

Fernanda Borges ◽

Maria J. Matos

Keyword(s):

Neurodegenerative Diseases ◽

Computer Aided Design ◽

New Technologies ◽

Chemical Properties ◽

Docking Studies ◽

New Drugs ◽

Drug Candidates ◽

New Drug ◽

Computer Aided ◽

Aided Design

: Computer-aided design of new drugs is an exponentially growing field, especially in the last decade. The support of theoretical tools may accelerate the drug discovery process, which is a long and very expensive journey. Tools as QSAR and docking calculations are on the top of the list for helping medicinal chemists to find more potent and selective molecules as potential leads for facing challenging diseases. Coumarins have been an important source of inspiration for the design of new drugs. Due to their chemical properties and their affinity to some targets, special attention has been paid to their role against neurodegenerative diseases. Therefore, the authors provide an overview of the scientific reports describing the research and development of new drug design tools supporting the discovery of coumarins as enzymatic inhibitors or receptor ligands involved in these diseases. This review emphasizes the rationale behind the design of new drug candidates, and particular attention is paid to the search for new leads over the last 10 years. QSAR and docking studies are discussed, as well as new technologies applied for the research in this field. The manuscripts discussed in this review have been collected from multiple electronic databases, including Pubmed, SciFinder, and Mendeley.

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