RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI

Dilara Eren; İsmail Yalçın

doi:10.33483/jfpau.688351

Review

RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI

Year 2020, Volume: 44 Issue: 2, 334 - 355, 31.05.2020

Dilara Eren , İsmail Yalçın

https://doi.org/10.33483/jfpau.688351

Cited By: 2

Abstract

Amaç: Bu derlemenin amacı Rasyonel İlaç Tasarımında kullanılan Moleküler Mekanik ve Moleküler Dinamik yöntemlerinin incelenmesi, yöntemlerin temelinin araştırılması, avantaj ve dezavantajlarının ortaya konmasını sağlamaktır.

Sonuç ve Tartışma: Yeni ilaç etken maddesi keşfi Farmasötik Kimya’nın temel ilgi alanıdır. Yeni ilaç etken maddesi keşfinde kullanılan Bilgisayar Destekli İlaç Tasarımı Yöntemleri günümüzde dikkat çeken yöntemlerdir. Bu yöntemler arasında kullanılan Moleküler Dinamik (MD) moleküller ve atomların bir araya gelerek etkileştikleri sitemin zaman içindeki gelişimini tahmin etmekte kullanılan bir bilgisayar simülasyon (benzetim) metodudur ve MD’nin dayandığı temel fikir moleküllerin zamana bağlı veya zamandan bağımsız mikroskobik davranışlarını simülasyonlarla gözlemleyerek oluşabilecek biyolojik aktiviteyi tahmin edilebilmeyi mümkün kılmaktır. 1970’lerden beri moleküler dinamik proteinler ve nükleik asitler gibi makromoleküllerin dinamik ve yapısal özellikleriyle ilgili çalışmalarda yaygın olarak kullanılmaktadır. Moleküler Mekanik ise moleküler sistemleri modellemek için klasik mekanik metotları kullanan, sistemin molekül içi ve moleküller arası enerjilerini “kuvvet alanları” oluşturarak hesaplama yöntemidir. Yeni ilaç etken maddesi keşfi zorlayıcı, zaman gerektiren ve pahalı bir süreçtir. Bu sürecin daha kolay hale gelmesi, daha az zaman ve emek harcayarak ve daha ucuz bir şekilde yürütülebilmesi için Moleküler Dinamik ve Moleküler Mekanik Yöntemler ağırlıklı çalışmalar yapılması yararlı olacaktır.

Keywords

moleküler dinamik, moleküler mekanik, moleküler modelleme, rasyonel ilaç tasarımı, yeni ilaç keşfi

References

1- Ramachandran, K.I., Deepa, G., Namboori, K.(2008). Computational Chemistry and Molecular Modeling, Springer, Coimbatore ,p1-3,p7, p205-207.
2- Schlick, T.(2010). Molecular Modeling and Simulation, Springer, New York,p3, p426-432.
3- Leach, A.R.(200).Molecular Modelling Principles and Applications, Pearson Educated Limited, Harlow,p9, p165-173, p353-355.
4- Hinchliffe, A.(2003).Molecular Modelling for Beginners, Wiley, Manchester, p2-4, p51-72, p123-130.
5- Cohen, N.C.(1996).Guidebook on Molecular Modeling in Drug Design, Elsevier, Basel, p1-6.
6- Mandal, S., Mandal, S. K. (2009). Rational drug design. European journal of pharmacology, 625(1-3), 90-100.
7- Hagedorn, G. A. (1980). A time dependent Born-Oppenheimer approximation. Communications in Mathematical Physics, 77(1), 1-19. 8- Jorgensen, W. L. (2004). The many roles of computation in drug discovery. Science, 303(5665), 1813-1818.
9- Van Drie, J. H. (2007). Computer-aided drug design: the next 20 years. Journal of computer-aided molecular design, 21(10-11), 591-601.
10- Śledź, P., Caflisch, A. (2018). Protein structure-based drug design: from docking to molecular dynamics. Current opinion in structural biology, 48, 93-102.
11- Bernardi, R. C., Melo, M. C., Schulten, K. (2015). Enhanced sampling techniques in molecular dynamics simulations of biological systems. Biochimica et Biophysica Acta (BBA)-General Subjects, 1850(5), 872-877.
12- Jyothirmayee C.A.(2014).Computer-aided drug design. Life Sciences International Research Journal, 1(1)
13- Shaw, D. E., Deneroff, M. M., Dror, R. O., Kuskin, J. S., Larson, R. H., Salmon, J. K., Eastwood, M. P. (2008). Anton, a special-purpose machine for molecular dynamics simulation. Communications of the ACM, 51(7), 91-97.
14- Durrant, J. D., McCammon, J. A. (2011). Molecular dynamics simulations and drug discovery. BMC biology, 9(1), 71.
15- De Vivo, M., Masetti, M., Bottegoni, G., Cavalli, A. (2016). Role of molecular dynamics and related methods in drug discovery. Journal of medicinal chemistry, 59(9), 4035-4061.
16- Borhani, D. W., Shaw, D. E. (2012). The future of molecular dynamics simulations in drug discovery. Journal of computer-aided molecular design, 26(1), 15-26.
17- Masetti, M., Rocchia, W. (2014). Molecular mechanics and dynamics: numerical tools to sample the configuration space. Frontiers in Bioscience, 19(1), 578-604.
18- Hollingsworth, S. A., Dror, R. O. (2018). Molecular dynamics simulation for all. Neuron, 99(6), 1129-1143.
19- Frenkel, D., Smit, B. (2002).Understanding Molecular Simulations, Academic Press,p.63-74.
20- Alder, B. J., Wainwright, T. E. (1957). Phase transition for a hard sphere system. The Journal of chemical physics, 27(5), 1208-1209.
21- Cheatham III, T. E.,Young, M. A. (2000). Molecular dynamics simulation of nucleic acids: successes, limitations, and promise. Biopolymers: Original Research on Biomolecules, 56(4), 232-256.
22- Binder, K., Horbach, J., Kob, W., Paul, W., Varnik, F. (2004). Molecular dynamics simulations. Journal of Physics: Condensed Matter, 16(5), S429.
23- Hassan Baig, M., Ahmad, K., Roy, S., Mohammad Ashraf, J., Adil, M., Haris Siddiqui, M., Choi, I. (2016). Computer aided drug design: success and limitations. Current pharmaceutical design, 22(5), 572-581.
24- Ferreira, L., dos Santos, R., Oliva, G., Andricopulo, A. (2015). Molecular docking and structure-based drug design strategies. Molecules, 20(7), 13384-13421.
25- Ganesan, A., Coote, M. L., & Barakat, K. (2017). Molecular dynamics-driven drug discovery: leaping forward with confidence. Drug discovery today, 22(2), 249-269.
26- Schatz, G. C. (1988). Quantum effects in gas phase bimolecular chemical reactions. Annual Review of Physical Chemistry, 39(1), 317-340.
27- Masetti, M., Rocchia, W. (2014). Molecular mechanics and dynamics: numerical tools to sample the configuration space. Frontiers in Bioscience, 19(1), 578-604.
28- van der Vaart, A., Bursulaya, B. D., Brooks, C. L., Merz, K. M. (2000). Are many-body effects important in protein folding?. The Journal of Physical Chemistry B, 104(40), 9554-9563.
29- Weiner, S. J., Kollman, P. A., Case, D. A., Singh, U. C., Ghio, C., Alagona, G., Weiner, P. (1984). A new force field for molecular mechanical simulation of nucleic acids and proteins. Journal of the American Chemical Society, 106(3), 765-784.
30- Nerenberg, P. S., Head-Gordon, T. (2018). New developments in force fields for biomolecular simulations. Current opinion in structural biology, 49, 129-138.
31- Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., Case, D. A. (2004). Development and testing of a general amber force field. Journal of computational chemistry, 25(9), 1157-1174.
32- Harder, E., Damm, W., Maple, J., Wu, C., Reboul, M., Xiang, J. Y.& Kaus, J. W. (2015). OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. Journal of chemical theory and computation, 12(1), 281-296.
33- Şener, E. A., Yalçın, İ. (2003). Farmasötik/Medisinal Kimya'da ilaç etken madde tasarım yöntemleri-1: kantitatif yapı-etki iİlişkileri analizleri (QSAR).p 2-6, p13-17
34- Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe, E. W. (2014). Computational methods in drug discovery. Pharmacological reviews, 66(1), 334-395.
35- Bone, R. G., Bader, R. F. (1996). Identifying and analyzing intermolecular bonding interactions in van der Waals molecules. The Journal of Physical Chemistry, 100(26), 10892-10911.
36- Hobza, P., Zahradník, R., Müller-Dethlefs, K. (2006). The world of non-covalent interactions: 2006. Collection of Czechoslovak Chemical Communications, 71(4), 443-531.
37- Buckingham, A. D., Fowler, P. W., Hutson, J. M. (1988). Theoretical studies of van der Waals molecules and intermolecular forces. Chemical Reviews, 88(6), 963-988.
38- Buckingham, A. D., Utting, B. D. (1970). Intermolecular forces. Annual Review of Physical Chemistry, 21(1), 287-316.

THE AIM OF IMPLEMENTATION OF THE MOLECULAR MECHANIC AND THE MOLECULAR DYNAMIC METHODS IN RATIONAL DRUG DESIGN

Year 2020, Volume: 44 Issue: 2, 334 - 355, 31.05.2020

Dilara Eren , İsmail Yalçın

https://doi.org/10.33483/jfpau.688351

Cited By: 2

Abstract

Objective: In this rewiev, ıt’s aimed to view the Molcular Dynamics and Molecular Mechanics methods to use in Rational Drug Design, research the basics, exhibit the advantages and disadvantages of these methods.

Result and Discussion: The discovery of drug active substance is the main research interest of the Pharmaceuthical Chemistry. Computer Aided Drug Design Methods are used in the discovery of new drug active substances are the methods attract attention. Molecular Dynamics is the computituonal simulation method to predict the development of the system that molecules and atoms interact together over time. The basic idea is to make it possible to predict the biological activity that may occur by observing the time dependent or time independent microscopic behavior of molecules. Since 1970’s it’s been widely used in studies of the dynamic and structural properties of macromolecules such as proteins & nucleic acids. Molecular Mechanics is the method of calculating the intramolecular and intermolecular energies of the system by creating force fields by using classical mechanical methods to model molecular systems. The discovery of new drug is challenging, time consuming and expensive process. These studies should be conducted in order to make this process easier, cheaper, to spend less time and effort.

Keywords

molecular dynamics, molecular mechanics, molecular modelling, new drug design, rational drug design

References

1- Ramachandran, K.I., Deepa, G., Namboori, K.(2008). Computational Chemistry and Molecular Modeling, Springer, Coimbatore ,p1-3,p7, p205-207.
2- Schlick, T.(2010). Molecular Modeling and Simulation, Springer, New York,p3, p426-432.
3- Leach, A.R.(200).Molecular Modelling Principles and Applications, Pearson Educated Limited, Harlow,p9, p165-173, p353-355.
4- Hinchliffe, A.(2003).Molecular Modelling for Beginners, Wiley, Manchester, p2-4, p51-72, p123-130.
5- Cohen, N.C.(1996).Guidebook on Molecular Modeling in Drug Design, Elsevier, Basel, p1-6.
6- Mandal, S., Mandal, S. K. (2009). Rational drug design. European journal of pharmacology, 625(1-3), 90-100.
7- Hagedorn, G. A. (1980). A time dependent Born-Oppenheimer approximation. Communications in Mathematical Physics, 77(1), 1-19. 8- Jorgensen, W. L. (2004). The many roles of computation in drug discovery. Science, 303(5665), 1813-1818.
9- Van Drie, J. H. (2007). Computer-aided drug design: the next 20 years. Journal of computer-aided molecular design, 21(10-11), 591-601.
10- Śledź, P., Caflisch, A. (2018). Protein structure-based drug design: from docking to molecular dynamics. Current opinion in structural biology, 48, 93-102.
11- Bernardi, R. C., Melo, M. C., Schulten, K. (2015). Enhanced sampling techniques in molecular dynamics simulations of biological systems. Biochimica et Biophysica Acta (BBA)-General Subjects, 1850(5), 872-877.
12- Jyothirmayee C.A.(2014).Computer-aided drug design. Life Sciences International Research Journal, 1(1)
13- Shaw, D. E., Deneroff, M. M., Dror, R. O., Kuskin, J. S., Larson, R. H., Salmon, J. K., Eastwood, M. P. (2008). Anton, a special-purpose machine for molecular dynamics simulation. Communications of the ACM, 51(7), 91-97.
14- Durrant, J. D., McCammon, J. A. (2011). Molecular dynamics simulations and drug discovery. BMC biology, 9(1), 71.
15- De Vivo, M., Masetti, M., Bottegoni, G., Cavalli, A. (2016). Role of molecular dynamics and related methods in drug discovery. Journal of medicinal chemistry, 59(9), 4035-4061.
16- Borhani, D. W., Shaw, D. E. (2012). The future of molecular dynamics simulations in drug discovery. Journal of computer-aided molecular design, 26(1), 15-26.
17- Masetti, M., Rocchia, W. (2014). Molecular mechanics and dynamics: numerical tools to sample the configuration space. Frontiers in Bioscience, 19(1), 578-604.
18- Hollingsworth, S. A., Dror, R. O. (2018). Molecular dynamics simulation for all. Neuron, 99(6), 1129-1143.
19- Frenkel, D., Smit, B. (2002).Understanding Molecular Simulations, Academic Press,p.63-74.
20- Alder, B. J., Wainwright, T. E. (1957). Phase transition for a hard sphere system. The Journal of chemical physics, 27(5), 1208-1209.
21- Cheatham III, T. E.,Young, M. A. (2000). Molecular dynamics simulation of nucleic acids: successes, limitations, and promise. Biopolymers: Original Research on Biomolecules, 56(4), 232-256.
22- Binder, K., Horbach, J., Kob, W., Paul, W., Varnik, F. (2004). Molecular dynamics simulations. Journal of Physics: Condensed Matter, 16(5), S429.
23- Hassan Baig, M., Ahmad, K., Roy, S., Mohammad Ashraf, J., Adil, M., Haris Siddiqui, M., Choi, I. (2016). Computer aided drug design: success and limitations. Current pharmaceutical design, 22(5), 572-581.
24- Ferreira, L., dos Santos, R., Oliva, G., Andricopulo, A. (2015). Molecular docking and structure-based drug design strategies. Molecules, 20(7), 13384-13421.
25- Ganesan, A., Coote, M. L., & Barakat, K. (2017). Molecular dynamics-driven drug discovery: leaping forward with confidence. Drug discovery today, 22(2), 249-269.
26- Schatz, G. C. (1988). Quantum effects in gas phase bimolecular chemical reactions. Annual Review of Physical Chemistry, 39(1), 317-340.
27- Masetti, M., Rocchia, W. (2014). Molecular mechanics and dynamics: numerical tools to sample the configuration space. Frontiers in Bioscience, 19(1), 578-604.
28- van der Vaart, A., Bursulaya, B. D., Brooks, C. L., Merz, K. M. (2000). Are many-body effects important in protein folding?. The Journal of Physical Chemistry B, 104(40), 9554-9563.
29- Weiner, S. J., Kollman, P. A., Case, D. A., Singh, U. C., Ghio, C., Alagona, G., Weiner, P. (1984). A new force field for molecular mechanical simulation of nucleic acids and proteins. Journal of the American Chemical Society, 106(3), 765-784.
30- Nerenberg, P. S., Head-Gordon, T. (2018). New developments in force fields for biomolecular simulations. Current opinion in structural biology, 49, 129-138.
31- Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., Case, D. A. (2004). Development and testing of a general amber force field. Journal of computational chemistry, 25(9), 1157-1174.
32- Harder, E., Damm, W., Maple, J., Wu, C., Reboul, M., Xiang, J. Y.& Kaus, J. W. (2015). OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. Journal of chemical theory and computation, 12(1), 281-296.
33- Şener, E. A., Yalçın, İ. (2003). Farmasötik/Medisinal Kimya'da ilaç etken madde tasarım yöntemleri-1: kantitatif yapı-etki iİlişkileri analizleri (QSAR).p 2-6, p13-17
34- Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe, E. W. (2014). Computational methods in drug discovery. Pharmacological reviews, 66(1), 334-395.
35- Bone, R. G., Bader, R. F. (1996). Identifying and analyzing intermolecular bonding interactions in van der Waals molecules. The Journal of Physical Chemistry, 100(26), 10892-10911.
36- Hobza, P., Zahradník, R., Müller-Dethlefs, K. (2006). The world of non-covalent interactions: 2006. Collection of Czechoslovak Chemical Communications, 71(4), 443-531.
37- Buckingham, A. D., Fowler, P. W., Hutson, J. M. (1988). Theoretical studies of van der Waals molecules and intermolecular forces. Chemical Reviews, 88(6), 963-988.
38- Buckingham, A. D., Utting, B. D. (1970). Intermolecular forces. Annual Review of Physical Chemistry, 21(1), 287-316.

There are 37 citations in total.

Details

Primary Language	Turkish
Subjects	Pharmacology and Pharmaceutical Sciences
Journal Section	Collection
Authors	Dilara Eren 0000-0001-9140-1317 İsmail Yalçın 0000-0002-7320-9994
Publication Date	May 31, 2020
Submission Date	February 12, 2020
Acceptance Date	May 5, 2020
Published in Issue	Year 2020 Volume: 44 Issue: 2

Cite

APA	Eren, D., & Yalçın, İ. (2020). RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI. Journal of Faculty of Pharmacy of Ankara University, 44(2), 334-355. https://doi.org/10.33483/jfpau.688351
AMA	Eren D, Yalçın İ. RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI. J. Fac. Pharm. Ankara. May 2020;44(2):334-355. doi:10.33483/jfpau.688351
Chicago	Eren, Dilara, and İsmail Yalçın. “RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI”. Journal of Faculty of Pharmacy of Ankara University 44, no. 2 (May 2020): 334-55. https://doi.org/10.33483/jfpau.688351.
EndNote	Eren D, Yalçın İ (May 1, 2020) RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI. Journal of Faculty of Pharmacy of Ankara University 44 2 334–355.
IEEE	D. Eren and İ. Yalçın, “RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI”, J. Fac. Pharm. Ankara, vol. 44, no. 2, pp. 334–355, 2020, doi: 10.33483/jfpau.688351.
ISNAD	Eren, Dilara - Yalçın, İsmail. “RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI”. Journal of Faculty of Pharmacy of Ankara University 44/2 (May 2020), 334-355. https://doi.org/10.33483/jfpau.688351.
JAMA	Eren D, Yalçın İ. RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI. J. Fac. Pharm. Ankara. 2020;44:334–355.
MLA	Eren, Dilara and İsmail Yalçın. “RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI”. Journal of Faculty of Pharmacy of Ankara University, vol. 44, no. 2, 2020, pp. 334-55, doi:10.33483/jfpau.688351.
Vancouver	Eren D, Yalçın İ. RASYONEL İLAÇ TASARIMINDA MOLEKÜLER MEKANİK VE MOLEKÜLER DİNAMİK YÖNTEMLERİN KULLANILMA AMACI. J. Fac. Pharm. Ankara. 2020;44(2):334-55.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.